ASSESSMENT OF RENAL FUNCTION AMONG HCV POSITIVE UNDER TREATMENT AT CHUB

Patrick NEMEYIMANA

Health and Medical researches

university of Rwanda

Health and Medicine, Volume 1, Issue 2, feb 04 2021, Pages 1–36,

More than 170 million people worldwide live with hepatitis C virus infection and 500,000 individuals died because of Hepatitis C Virus linked with liver disease in 2010. HCV infection and the kidney has a strong relationship where around 10-16 % of the patients with hepatitis C viral infection may develop renal impairment. In Rwanda, the burden of Hepatitis C infections reaches to 3.1% out of 11.9 million people. Even though Rwanda has set to eliminate HCV in 2019, there are still challenges in managing and monitoring HCV patients with renal dysfunction. The aim of this research project was to determine the prevalence of renal dysfunction in Hepatitis C patients under treatment. A descriptive cross-sectional design was used to assess the renal function among 76 HCV positive participants. Venous blood was collected for creatinine and urea testing coupled with detection of albumin in urine samples.

Among 76 participants, 25(32%) were males and 51(61.10%) were females. The prevalence of renal dysfunction was 28.9%. Females were more susceptible to renal dysfunction than males with a prevalence of 23.68%. The occurrence of renal impairment was particularly in participants above 59 age with a prevalence of 22.78%.

CHAPTER 1. INTRODUCTION

1.1. DEFINITION OF KEY TERMS

Renal dysfunction: Refers to the medical condition in which the kidneys are no longer functioning and may be divided into acute and chronic kidneys failure(Scanlon, 2017).

Hepatitis C: It is an inflammation of the liver due to the Hepatitis C Virus, which is usually spread via infected blood like blood Transfusion, hemodialysis…(Lanini , 2016).

Cryoglobulins: Are immunoglobulins, which reversibly precipitate in serum at low temperatures. There are classified into 3 types(Shetty, Kirti, 2016).

Glomerulonephritis: Talk about a sterile, inflammation process that distresses the glomerulus and is related to the finding of blood, protein, and cast in the urine(Susan King Strasinger, 2013).

1.2. BACKGROUND

More than 170 million people worldwide live with hepatitis C viral infection, and 500,000 people died of HCV-related liver disease in 2010(Gonzalez et al., 2015). But also there are etiological links to numerous extra-hepatic medical condition with renal disorders(Perico et al., 2015). There is a strong relationship between hepatitis C viral infection and kidney.  Around 10 to 16% of the patients with hepatitis C virus infection develop into renal impairment, and the prevalence of HCV infection in patients with renal dysfunction is higher than that of the general population(Lens and Llovet, 2017).

Chronic renal diseases and HCV are a common and potentially serious medical problem throughout the world (Perico et al., 2009). Several risk factors particularly enhance the development of  renal dysfunction like  HIV co-infection, HBV co-infection, metabolic disorder, tobacco use, alcohol use and viral related factors (Shetty, Kirti, 2012).Therefore, the prevalence of HCV in patients on hemodialysis is higher than the prevalence that is found among the general population. Research published in 2013 by Goodkin et al on 49,000 patients on dialysis from diverse countries around the world indicates that 9.5% on hemodialysis the prevalence ranged between 3.3-16.8%. Furthermore, hepatitis C viral infection  has a higher morbidity and mortality risk to patients with kidney diseases (Goodkin et al., 2013). 

However, it was reported that the risk of death is not related to liver death but was also associated with cardiovascular disease with an (F.Fabrizi and V.Dixit, 2012). Chronic HCV has been both, directly and indirectly, associated with the development of Chronic Kidney Disease(Cacoub et al., 2014). Directly, HCV has been associated with the development of glomerulonephritis, via increased autoantibody IgM production with rheumatoid factor activity, leading to mixed cryoglobulinemia and deposition into glomerular capillary and tubules. Indirectly, HCV has been associated with an increased risk of insulin resistance and atherosclerosis, which are important CKD risk factors (Rossi et al., 2017).

In the USA, 4.1 million persons were anti-HCV positive, most of whom were older than 45 years(Lanini et al., 2016). Patients on chronic hemodialysis  are at high risk for HCV infection and it appears to be related to the time that the patient has been receiving dialysis as well as the number of blood transfusions received(Barsoum, William and Khalil, 2017).

In Europe; recent study covering the geographical area as defined by the WHO i.e. including the former USSR republics has estimated that the prevalence of HCV varies between 2.4% for Western and Central Europe and 2.9% for Eastern Europe(Negro, 2014). The global population of this area is approximately 740,000,000 persons, leading to an estimation of the HCV infected pool of more than 19,000,000 persons, a number to be adjusted in the future given the limited evidentiary support, especially for some countries in Central Europe and for the whole Eastern European bloc(Negro, 2014).

Rwanda, a low-income country as classified by the World Bank and has now increased its attention to the hepatitis C epidemic. The sero-prevalence of HCV antibody has most recently been estimated to be 3.1% within the general Rwandan population of 11.9 million people and 4.7% (5470) among the 116 868 people living with HIV. Whereas hepatitis C prevention efforts have been increasing, we found no existing surveys or qualitative data regarding attitudes, knowledge or beliefs towards viral hepatitis in the general population in Rwanda, reflecting an overall lack of published literature on this topic in sub-Saharan Africa. In addition, the causes of HCV transmission in Rwanda are largely unknown but are assumed to include past traditional medical practices, unsafe injection practices during and before the 1970s, exposure to contaminated blood during the Rwandan genocide of 1994 and blood transfusions before 1999(Mbituyumuremyi, Ilo and Nuil, 2017).

More than 170 million people are chronically infected with the hepatitis C virus (HCV) while the prevalence of chronic kidney disease is between 10%-16% worldwide (Barsoum, William and Khalil, 2017). The prevalence of HCV positive among hemodialysis patients can vary from 5% to 60% from a different region in the world(Gonzalez et al., 2015). In Taiwan, the prevalence of CKD among those who are seropositive for hepatitis C was 16.5% (Dalrymple et al., 2014).    

In sub-Saharan Africa, the number of estimated deaths due to HCV almost doubled from 53,000 in 1980, to 103,000 in 2010. In the southern region of Africa, the prevalence of HCV associated mortality is about a half that of the central, eastern and western regions of Africa. Eastern region, Uganda was ranked in the top 10 countries with a high HCV mortality rate in 2010(Norbeto perico et al, et al 2015).

In Rwanda, the burden of this infection reaches to 3.1% out of 11.9 million people(Mbituyumuremyi, Ilo and Nuil, 2017). Above all that, around 10–16% of the patients with HCV infection progress to renal impairment, and the prevalence of HCV infection in patients with renal dysfunction is higher than the general population (Lens and Llovet, 2017).

Even though Rwanda has set the elimination targets of HCV, there are still challenges in managing and monitoring HCV patients with renal dysfunction(Mbituyumuremyi, Ilo and Nuil, 2017). Specifically, the attention in monitoring HCV patients with renal dysfunction has been less in various health settings in Rwanda. The proposed study aimed at determining the prevalence of renal dysfunction and associated risk factors among HCV positive patients under treatment attending Butare University Teaching Hospital.

1.4. OBJECTIVES

1.4.1 Main Objective

To determine the prevalence of renal dysfunction and associated risk factors among HCV positive patients under treatment attending Butare University Teaching Hospital.

1.4.2. Specific objectives

1. To determine the prevalence of renal dysfunction among HCV positive patients under treatment attending Butare University Teaching Hospital according to age and sex.

2. To assess the risk factors of renal dysfunction among HCV positive patients under treatment attending Butare University Teaching Hospital by using questionnaire.   

1.5. RESEARCH QUESTIONS

1. What isthe prevalence of renal dysfunction among HCV patients attending Butare University teaching Hospital(CHUB) according to age and sex?

2.   What are the associated risk factors for renal dysfunction among HCV positive patients attending Butare University teaching Hospital(CHUB) by using HIV, HBV coinfection, alcohol consumers and smoking?

1.6. SIGNIFICANCE OF STUDY

Most studies have shown that patients with chronic kidney diseases and HCV have higher mortality risk than only those with chronic renal diseases. The findings of this study complimented the existing information on renal dysfunction among HCV positive patients attending CHUB. Therefore, we hope that the findings of this study will provide researchers the information on careful monitoring of HCV positive patients regarding the risk factors. 1.7 MOTIVATION OF STUDY

The motivation of this research was the willingness to provide information that can help in management and treatment of renal failure among HCV Positive patients. Recent years many study showed the intense relationship between HCV and renal dysfunction as a result of extrahepatic manifestation.

Proving information about the assessment of renal function among HCV Positive patient would help in setting evidence based strategies for management of renal failure among HCV Positive patient.

1.8. SUBDIVISION OF STUDY

The present study is divided into three main chapters. Chapter one comprises definitions of key terms, background to the study, problem statement, research hypothesis, objectives, significance of the study, motivation of the study and subdivision of the study and study subdivision of the study, chapter two is literature review that entitled the present literatures describing the relationship between renal dysfunction and HCV positive patients. The chapter 4 presents results. Chapter 5 is then comprised of discussion and recommendation.  

CHAPTER 2. LITERATURE REVIEW

The kidney is an important component of the HCV clinical syndrome, besides the liver, musculoskeletal, immune and hematopoietic systems and the skin. This notorious viral infection imposes itself as a cause of kidney disease, a major risk in dialysis wards, and a significant threat in renal transplantation referring to Pereira et al.  As many works of literature had shown, 10 to 16% of the patients with hepatitis C virus infection develop into renal impairment (Lens and Llovet, 2017).

2.1. Epidemiology

In the USA, 4.1 million persons were anti-HCV positive, most of whom were older than 45 years of age  (Lanini et al., 2016). In Europe; recent study covering the geographical area as defined by WHO i.e. including the former USSR republic has estimated that the prevalence of HCV varies between 2.4% for Western and Central Europe and 2.9% for Eastern Europe(Negro, 2014).

The global population of this area is approximately 740,000,000 persons, leading to an estimation of the HCV infected pool of more than 19,000,000 persons, a number to be adjusted in the future given the limited evidentiary support, especially for some countries in Central Europe and for the whole Eastern European bloc(Negro, 2014). In sub-Saharan Africa, the number of estimated deaths due to HCV almost doubled from 53,000 in 1980, to 103,000 in 2010(Mark W Sonderup et al., 2017).

According to the 2014 United States Renal Data System (USRDS) report, Taiwan had the greatest incidence of end stage renal disease (ESRD). CKD is more prevalent in the elderly population. However, while young patients with CKD typically experience progressive loss of kidney function, 30% of patients over 65 years of age with CKD have stable disease.

Renal dysfunction is the inability of the kidney to perform its normal functions in terms of regulating fluid and electrolyte balance, controlling blood pressure through fluid volume and the renin-angiotensin system, eliminating nitrogenous and other waste products, governing the red blood cell count through erythropoietin synthesis, and directing parathyroid and skeletal function through phosphate elimination and activation of vitamin D(Ladino, Pedraza and Roth, 2016).

2.2. Relationship between HCV and Renal Function

The kidney is an important component of the HCV clinical syndrome, besides the liver, the musculoskeletal, immune and hematopoietic systems and the skin (Barsoum, William and Khalil, 2017). Persons infected with hepatitis C virus (HCV) can develop kidney disease as a result of extra-hepatic manifestation of HCV(Sanchez and Ward, 2012). The main target of chronic HCV is the liver cells (hepatocytes), but there are many diverse extra-hepatic manifestations of chronic HCV which are caused by the activation of the host immune system in response to the infection. The extra-hepatic manifestations that have clearly been shown to be associated with HCV are induced by formation of type II cryoglobulins due to chronic viral antigen stimulation of the host immune system(Shetty, Kirti, 2009).

Chronic hepatitis C virus has the potential to affect wide-ranging organ systems, including the kidneys, the skin, the hematological system, and even cause autoimmune disease and diabetes. When it comes to the kidneys, hepatitis C tends to affect the glomerulus of the kidneys in many ways and creating different disease processes(Cacoub et al., 2014). This realization that hepatitis C can has a major impact on kidney function and cause kidney disease (Shetty, Kirti, 2009)

2.3. Cause of Renal Dysfunction in HCV Positive Patient

Hepatitis-C Virus (HCV) infection can induce kidney injury, mostly due to formation of immune complexes and cryoglobulins, and possibly to a direct cytopathic effect. It may cause acute kidney injury (AKI) as a part of systemic vasculitis, and augments the risk of AKI due to other etiologies(Barsoum, William and Khalil, 2017). The cause of renal impairment in HCV-positive patients is the presence of mixed cryoglobulinemia, which is indicated by an immune complex-mediated vasculitis affecting small vessels in glomerulus, as a result of a non-malignant clonal stimulation of B lymphocytes generating cryoglobulins(Lens and Llovet, 2017).

Hepatitis C virus can cause kidney disease in four ways: glomerular immune complex deposition; direct viral invasion of the renal parenchyma; renal complications of its extra renal (e.g. hepatic) manifestations; and nephrotoxicity of drugs used for its treatment. These mechanisms often interact in the pathogenesis of several acute and chronic clinical renal syndromes. (Barsoum, William and Khalil, 2017).

2.4. Complications of HCV on the Kidney

HCV is one that can cause acute kidney disease, which often progresses to acute kidney injury (AKI), in patients with acute or fulminant cryoglobulinemic vasculitis(Susan King Strasinger, 2008). Chronic HCV infection, can be a significant risk factor for AKI in patients with dehydration, sepsis, or advanced liver injury(Cacoub et al., 2014).

It is a systemic disease reported in 5% –15% of HCV-infected positive patients. It is characterized by multi-organ involvement, mainly affecting the lungs, kidneys, skin, musculoskeletal system and peripheral nerves(Carl a.burtis, 2008). The fundamental lesion is endothelial injury, small vessel necrosis, perivascular inflammation with lymphocytic and neutrophilic infiltration and luminal occlusion by cryoglobulins and fibrin thrombi.

In the kidneys, this leads to focal fibrinoid necrosis of the glomerular tufts, often with crescent formation.The renal tubules are affected by ischemic and inflammatory lesions and contain hyaline and blood casts. The interstitium is edematous and infiltrated with inflammatory cells. The ureteric and bladder mucosa may display vasculitic purpuric lesions. HCV-associated chronic kidney disease may be attributed to cryoglobulinemia, viral antigen-antibody complexes and possibly a direct viral cytopathic effect.

Compared to the general population, HCV-infected patientsare at many-fold risk of developing AKI of diverse, apparently unrelated etiology(Barsoum, William and Khalil, 2017).

HCV-associated chronic kidney disease may be attributed to cryoglobulinemia, viral antigen-antibody complexes and possibly a direct viral cytopathic effect(Barsoum, William and Khalil, 2017).

This has the strongest association with HCV and near complete association with type II cryoglobulinemia. HCV RNA, in patients with MPGN, is found in antigen–antibody complexes in the bloodstream and glomeruli. HCV has also been reported to be associated to a lesser degree with membranous and proliferative glomerulonephritis, focal segmental glomerular sclerosis, fibrillary and immunotactoid glomerulopathy. MPGN usually is a late manifestation of HCV-associated cryoglobulinemia and typically presents with hypertension, nephrotic-range proteinuria, microscopic hematuria, rapid decline in renal function, or chronic renal insufficiency.  Renal manifestations are a leading contributor to morbidity and mortality in HCV-related cryoglobulinemia(Shetty, Kirti, 2009).

There are sub-endothelial depositions in the glomeruli consisting of IgM with rheumatoid factor, IgG, and complement. Membranoproliferative glomerulonephritis (MPGN) is marked by two different alterations in the cellularity of the glomerulus and peripheral capillaries. Type 1 displays increased cellularity in the subendothelial cells of the mesangium (interstitial area of Bowman’s capsule), causing thickening of the capillary walls, whereas type 2 displays extremely dense deposits in the glomerular basement membrane. Many of the patients are children, and the disease has a poor prognosis, with type 1 patients progressing to the nephrotic syndrome and type 2 patients experiencing symptoms of chronic glomerulonephritis(Susan King Strasinger, 2008). The laboratory findings are variable; however, hematuria, proteinuria, and decreased serum complement levels are usual findings.

HCV antigen may be demonstrated in the glomeruli without detectable antibodies by enzyme-linked immune-sorbent assay (ELISA), or viral replication in peripheral blood by conventional PCR.  It is possible to explain that the direct endothelial cytopathic effect may explain the accelerated atherosclerosis observed in HCV-infected patients. The later has been partly blamed for the relatively fast progression of CKD in HCV positive patients, regardless of the etiology(Barsoum, William and Khalil, 2017).

HCV infection accounts for over 90% of cases with Type II mixed essential cryoglobulinemia. About 30% of affected patients ultimately develop mesangiocapillary glomerulonephritis. Cryoglobulins precipitate in the glomerular mesangium during their ‘‘macromolecular trafficking” owing to the affinity of the IgM Kappa Rheumatoid Factor (j-RF) to cellular fibronectin present in the mesangial matrix(Barsoum, William and Khalil, 2017). By virtue of their integral complement component, they attach to complement receptors and initiate a mesangial inflammation. Complement also activates the glomerular endothelium, which adheres to the circulating cryoglobulins that deposit in the capillaries providing the main histological diagnostic clue. Endothelial injury includes the peritubular capillaries leading to an interstitial inflammatory response, which eventually leads to fibrosis and largely accounts for impaired function(Cacoub et al., 2014).

Same study showed that in patients with concomitant infection with Schistosoma mansoni and HCV, both being frequently endemic in the same geographical regions. The glomerular lesions are characterized by a combination of mesangial expansion, amyloid deposits, and capillary cryoglobulin and fibrin deposits(Al-rabadi et al., 2018). The amyloid component is the hallmark of this co-infection, being attributed to an imbalance in between the release and the re- uptake of AA protein by the macrophages. The clinical presentation of cryoglobulinemic glomerulonephritis is a combination of the Meltzer triad (comprising skin vasculitis, arthralgia and myalgia) along with manifestations of chronic kidney disease. The latter vary from asymptomatic hematuria and/or proteinuria at one end of the spectrum, to progressive renal failure on the other(Shetty, Kirti, 2009).

Mesangiocapillary glomerulonephritis may be associated with HCV infection despite the absence of circulating cryoglobulins in which case HCV-IgG immune complexes are responsible for the glomerular pathology. Viral non-structural protein-3 (NS3) was detected in the glomerular deposits which were linear or granular along the capillary walls and in the Mesangium(Rena K. Fox, David H. Spach, 2018).

2.5.      Treatment of HCV.

Before the treatment of HCV patients with renal impairment was quiet difficult because most of the anti-retrovirals used were harmful and could worsen the renal complications according to (Lens and Llovet, 2017) . The invention of direct acting antivirals (DAAs) in combination with ribavirin has sparked enthusiasm in treating HCV patients with chronic kidney disease(Al-rabadi et al., 2018).  The current treatment for HCV patients worldwide is DAAs but those with renal impairment take DAAs in combination with ribavirin though requires special consideration and careful monitoring(Goodkin et al., 2013).

Table2.1. Treatment Options for Hepatitis C Infection (Rwanda Ministry of Health, 2013).

Drugs Available for HCV Treatment
MoleculesClassRecommendation
RibavirinNucleoside Analog or Nucleoside Reverse Transcriptase InhibitorRecommended
Interferon-alpha-2aInterferonRecommended
Interferon-alpha-2bInterferonRecommended
Pegylated interferon-alpha2aInterferonRecommended
Pegylated interferon-alpha2bInterferonRecommended
BoceprevirProtease InhibitorRecommended
TelaprevirProtease InhibitorRecommended

Many studies demonstrated that renal dysfunction is higher in women than in men(Kazanciog, 2013). Several studies performed in the United States have confirmed an increased risk for the development of renal failure in African Americans compared with Caucasians. Renal function decreases with age in both men and women. Among the elderly population, more than one-half of the subjects screened had CKD stages 3–5 (GFRo60ml/min per 1.73m2) according to the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines(Kazanciog, 2013).

Thus, the elderly population is more prone to develop CKD after various renal insults. Also one of the strongest yet modifiable risk factors for renal failure in the twenty-first century is obesity(Gonzalez et al., 2015). Obesity may contribute to the pathogenesis of kidney damage through inflammation, oxidative stress, endothelial dysfunction, prothrombotic state, hypervolemia, and adipokine derangements(Kazanciog, 2013).

Smoking can also increase the renal failure risk through the pro-inflammatory state, oxidative stress, prothrombotic shift, endothelial dysfunction, glomerulosclerosis and tubular atrophy. Diabetes mellitus (DM) not left out, is the leading cause of kidney disease in both developed and developing countries(Kazanciog, 2013). Mechanisms that lead to kidney disease in diabetes include hyperfiltration injury, advanced glycosylation end products, and reactive oxygen species.

Lastly hypertension has long been a defined risk factor for both kidney diseases. Systemic hypertension is transmitted to intra-glomerular capillary pressure leading to glomerulosclerosis and loss of kidney function; thus variable risk of impaired renal function has been reported among hypertensive subjects,and other risk factor are HIV,HBV coinfection and alcohols(Gonzalez et al., 2015).

2.9. Renal Function Tests

This brief review of renal physiology shows that there are many metabolic functions and chemical interactions to be evaluated through laboratory tests of renal function. These tests primarily evaluate glomerular function by assessing the glomerular filtration rate(Arneson, 2012). There are many renal functional test; urea, creatinine, GFR, EGFR, electrolyte, minerals, albuminuria. Our study will basically focus on three main renal function tests; creatinine, urea, and as well albumin.

2.9.1. Blood urea nitrogen(BUN)

Urea, an end product of protein metabolism that is produced in the liver. From there, it travels through the blood and is excreted by the kidneys(Susan King Strasinger, 2010). Urea is filtered at glomerulus, where the tubules reabsorbed approximately 40%. Thus under normal conditions, urea clearance is about 60% of the true GFR. Normal values for BUN range from 8mg/dl to 18 mg/dl, Decreased BUN levels occurred with significant liver disease. Increased BUN levels may indicate renal disease(Arneson, 2012).

2.9.2. Serum creatinine

It is the metabolic break down product of muscle creatinine phosphate, has a relatively constant level of daily productions. Blood levels very little in a given individual. Creatinine is excreted by glomerular filtration and tubular secretion(Cheesbrough, 2010). Creatinine clearance parallels the GFR within a range of ±10% and is a more sensitive indicator of renal damage than BUN levels because renal impairment is almost the only cause of an increase in the serum creatinine levels(Susan King Strasinger, 2012). Normal values for serum creatinine range from 0.6 to 1.2 mg/dl. Values vary with the amount of muscle mass‐a value of 1.2 mg/dl in a muscular athlete may represent normal renal function, whereas the same value in a small, sedentary person with little muscle mass may indicate significant renal impairment(Arneson, 2012).

Generally, the serum creatinine value doubles with each 50% decrease in GFR. For example, if a patient’s normal serum creatinine is 1mg/dl, 1mg/dl represents 100% renal function, 2mg/dl represents 50% function and 4mg/dl represents 25% function(Carl a.burtis, 2015).

2.9.3. Estimated GFR

National Kidney Foundation recommends a EGFR be calculated each time a serum creatinine is reported; Want to detect chronic renal disease earlier, redicts GFR based on patient age, sex, body size, race, serum creatinine and Do not need to collect timed urine which is better for patient(Arneson, 2012).The formula used

EGFR (ml/min) = (140 -age) x (Weight in kg)x (0.85 if female)

                              72 x Serum creatinine in mg/dl

2.9.4. Albuminuria

Albumin is a type of protein that is normally found in the blood. Albuminuria is a pathological condition where the protein albumin is abnormally present in the urine. It is a type of proteinuria. Albumin is a major plasma protein; in healthy people, only trace amounts of it are present in urine, whereas larger amounts occur in the urine of patients with kidney disease(Carl a burtis, 2015). A normal amount of albumin in your urine is less than 30 mg/g.   Anything above 30 mg/g may mean you have kidney disease, even if your GFR number is above 60 (Arneson, 2012).

CHAPTER 3. METHODOLOGY

3.1. INTRODUCTION

This chapter describes the methodology we used for the study; Study area, study design, study population, sample size, Sampling strategy, data collection methods, data analysis, limitation of the study and ethical consideration.

3.2. STUDY AREA

The study was carried out at Butare University Teaching Hospital located in the southern province, Huye district and Ngoma sector in Butare city near UR Huye campus.

3.3 STUDY DESIGN

A descriptive cross-sectional design was used to describe the assessment of renal function among HCV positive patient under treatment attending CHUB.

3.4. STUDY POPULATION

The study was conducted on HCV positive patients under treatment attending Butare University Teaching Hospital.

INCLUSION CRITERIA: all HCV positive patients under treatment attending Butare University Teaching Hospital.

EXCLUSION CRITERIA: all HCV negative attending Butare University Teaching Hospital.

3.5. SAMPLE SIZE

The study sample size was 138 participants who met the design criteria within the given data collection period.

The calculation of 138 as the sample size was determined using formula(Rosner, 2010):

Where

n=minimum sample size

z=standardized normal deviation which is equally to 1.96 (at 95% confidence interval)

P= estimated population prevalence equal to 10% (Rwanda ministry of health, 2015).

e= estimated error equal to 0.05

n=

n=138

3.6. SAMPLING STRATEGY

Written informed consent and printed questionnaires were used. Purposive sampling method was also used until obtaining sample size according to the inclusion criteria.

3.7. DATA COLLECTION METHOD AND PROCEDURE

This study was conducted at BUTH laboratory department precisely in biochemistry. Data was collected using a laboratory diagnostic test of blood serum urea and creatinine, and urine sample for albuminuria.

3.7.1. Specimen collection

Two samples were collected: blood sample by veinepuncture in a plain tube and a voided random urine sample.

Materials

Gloves, Needle, Test tube, Cotton(pad), Vacutainer, Lab coat, Marker, Phlebotomy chair, Log book, Pad containing Alcohol (conc 70), a tube holder. Sharp container waste bin, Waste bin, sterile urine collection container, Soap pads or towelettes, Labels.

3.7.2. Principle of the method for serum urea measurement

Urea is hydrolyzed by the action of the urease to produce ammonia and carbon dioxide. The ammonia reacts with hypochlorite and phenol in the presence of  sodium nitroprusside to form indophenol, which in alkaline medium give intense blue color. The intensity of the color formed is directly proportional to the concentration of urea in the sample.

Materials

Micropipettes of 200 µl, 50 µl, spectrophotometer, incubator, centrifuge, becher, reagent, tube holder, marker and gloves.

3.7.3. Procedure for serum urea measurement

We referred to the kit protocol method, following manufacturer’s instructions and prepared reagents and performed assays.

3.7.4. Principle of the method of creatinine measurement

Creatinine in alkaline solution reacts with picric acid to form a colored complex. The intensity of the color formed is directly proportional to the creatinine concentration in the sample.

Chemical method: Jaffe reaction

 

3.7.5. Procedure for serum creatinine measurement (chemical method)

We referred to the kit protocol method, following manufacturer’s instructions and prepared reagents and performed assays.

3.7.6 Procedure for eGFR measurement

After measurement of creatinine, we measured eGFR by using this formula

EGFR (ml/min) = (140 -age) x (Weight in kg) x (0.85 if female)

                              72 x Serum creatinine in mg/dl

3.7.6. Principle for measurement of albumin in the urine

Albumin reagent strips utilize the dye (3′,3′′, diodo-4′,4′′- dihydroxy-5′,5′′-dinitrophenyl)-3,4,5,6-tetra-bromosulphonphtalein (DIDNTB), which has a higher sensitivity and specificity for albumin. The DIDNTB strips can measure albumin between 8 and 20 mg/dL (80 to 200 mg/L). Colors range from pale green to aqua blue.

3.7.7. Procedure for urine albumin measurement

Take the strip tests put in a sample for 1min then remove the strip test and check the color change and record the results.

3.8. Data analysis

Data were analysed by using descriptive statistical analysis, Microsoft excel and SPSS and results were presented by using frequency table with percentages. Tables and figures showing the association between variables was used to interpret the data.

3.9. Problem and limitations.

1. Both ethical clearance from University and approval of data collection by BUTH were not submitted to us on time which were some of the reasons why we failed to achieve our sample size (138).

2. The data collection period was also generally short regardless of other factors.

3. The number of HCV positive patients who attend BUTH is generally low due to unknown reasons.

3.10. Ethical consideration

The permission to conduct the study was obtained from the Institutional Review Board, UR-CMHS. Then, we went on to seek permission to carry out the study from ethical committee of BUTH. We specifically gave enough explanation to the laboratory staff members in their respective departments about the study (objectives, duration and importance to participate) and all allowed to work properly with us. Those who agreed to participate signed a consent form and were properly explained about their confidentiality. The participation was voluntary and information gathered was kept safely, no names and patient ID presented on results.

CHAPTER 4: RESULTS

This chapter includes the findings of data collected from 76 participants in HUYE district, 25(32%) were male and 51(61.10%) were female. All participants were HCV positive. The data presentation of participant’s responses is represented using tables and short descriptions are added after each table.

Table 4.1. Prevalence of renal dysfunction among HCV positive patients according to the age.

AGE * eGFR Cross tabulation
 EGFR ml/minTotal
<60>60
AGE years20-29246
30-39033
40-49077
50-5921820
>59182240
Total225476
P value = 0.013

The table above displays the frequency between age and EGFR. In 22 participants who had low EGFR (abnormal EGFR), 18(81.81%) were greater than 59 years. Generally, the affected group belongs to those with greater than 59 years of age. The P value =0.013 show strongly significant, increase in age increase probability of developing renal failure (P value<0.05 indicate significance).

The prevalence of renal dysfunction among HCV positive patients on treatments was 28.89%, and 22.784% of the later prevalence were above 59 years.

Table 4.2: Prevalence of renal dysfunction among HCV positive patients on treatments according to gender.
Gender * eGFR Cross tabulation
 eGFR ml/minTotal
<60>60
SEXMale42125
Female183351
Total225476
P value=0.086

The table represents the frequency between EGFR and gender.

The prevalence of all participant was 28.89%, among of them, 23.68% were female, and whereas 5.26%were male.  P value=0.086 which is no significance.

Table 4. 3: Associated risk factors of renal dysfunction Among HCV positive patients.

EGFR(ml/min),n=76Total (%)P value
FactorsDescriptionLow(<60ml/min)High(>60/min)
HIVYES0(0%)0(0%)0(0%)p value= a
No22(28.89%)54(71.05%)76(100%)
HBVYES0(0%)0(0%)0(0%)P value= a
No22(28.89%)54(71.05%)76(100%)
SMOKINGYES4(5.22%)3(3.94%)7(9.16%)P value=0.08
No18(23.68%)51(67.10%)69(90.78%)
ALCOHOLYES3(3.94%)7(9.21%)10(13.15%)P value=0.93
No19(25%)47(61.81%)66(86.84%)

P value =a means no statistics are computed because HIV and HBV are constant. There is no coinfection between HCV and HBV or HIV.

In the table above, show the same associated risk factor with renal dysfunction. No HIV and HBV coinfection found on the participant. Among 76 participants,4(5.22%) smokers had low EGFR, and 3(3.94%) who were consuming alcohol had low EGFR. The P value of smoking and EGFR P Value= 0.08 had no significance (P value<0.05 indicate significance). The P value of alcohol consumer’s P value=0.93 had no significance (P value<0.05 indicate significance).

CHAPTER 5: DISCUSSION

Though, the association of hepatitis C virus and renal function is still measured in extra-hepatic manifestations but it also needs a special attention as around 10 to 16% of the patients with hepatitis C virus infection develop into renal impairment, and the prevalence of HCV infection in patients with renal dysfunction is higher than that of general population(Lens and Llovet, 2017).

It has been approved by many works of literature that HCV positive patients are likely to progress to renal complications as it is associated with the development of glomerulonephritis, through increased autoantibody IgM production with rheumatoid factor activity leading to mixed cryoglobulinemia and the deposition into glomerular capillary and tubules(Cacoub et al., 2014). Infection with HCV has been implicated as being causative in most patients with mixed cryoglobulinemia and several histologic forms of glomerular injury, including membranoproliferative and membranous glomerulonephritis(Barsoum, William and Khalil, 2017). 

This study is in line with studies that had proved using direct-acting antivirals in patients with CKD and those on dialysis are showing excellent safety and efficacy as well. The prevalence of HCV and renal impairment may vary from 5% to 60% in different regions though there is no scientific proof to this(Ladino, Pedraza and Roth, 2016).

Many studies recommend that immediately after diagnosis with HCV, the patient has to be requested some of the renal function tests to assess if this infection has negatively affected the kidneys. Treating HCV patients was quiet difficult as most HCV regimens silently could lead to some extra-hepatic manifestations including renal impairment but an invention of direct acting anti-retroviral therapy effectively treat HCV without adverse effects on the kidneys(Cacoub et al., 2014). 

The results of this study showed that the prevalence of renal dysfunction among HCV positive patients on treatments attending Butare university teaching hospital (CHUB) was P=28.94% which is higher than the prevalence shown by Lens et al  (2017) in study conducted at Barcelona in Spain, where around 16% of the patients with hepatitis C virus infection develop into renal dysfunction. The prevalence increase because the sample size was small(Lens and Llovet, 2017).

Among of the Prevalence of this study according to age,22.784% were above 59 years which was more tend to have renal dysfunction. Which indicate that Renal function decreases with age in both men and women as the same as result in the study conducted by (Kazanciog, 2013) in Istanbul, Turkey where Among the elderly population, more than one-half of the subjects screened had renal dysfunction(GFR>60 ml/min per 1.73m2)(Kazanciog, 2013).

According to the risk factors according to the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines in 2016 showed that the elderly population has more prevalence of renal functions than others(Kazanciog, 2013).The prevalence in this study P=23.68% were female, and P=5.26%were male which indicate women affected than men. According to the previous study study done by Rumeyza (2013) demonstrated that kidney dysfunction is higher in women than in men (18.4 vs. 12.8%) in Turkey (Rumeyza,2013).

Regards to risk factors, in this this study, no HIV and HBV coinfection found on the participant. Among 76 participants,4(5.22%) who was smoking had low EGFR, this number was low compared with the study conducted by Xia J.et al (2017) in chine show that most smoked cigarettes so with hepatitis C was associated with an increase in serum creatinine by 31%.  The 3 (3.94%) who was consuming alcohol had low EGFR, the previous study EGFR the more you take alcohol can increase risk of renal failure. The P value of smoking and EGFR P Value= 0.08 had no significance (P value<0.05 indicate significance).The P value of alcohol consumer’s 0.93 had no significance(Kazanciog, 2013).

CHAPTER 6. CONCLUSION AND RECOMMENDATION

6.1 CONCLUSION

On the basis of these findings, there is indeed a relationship between HCV and kidney dysfunction as also most of other studies came up with. During this study most of the patients with HCV tended to have high levels of some of the kidney function tests (those that may indicate the abnormal function of the kidney), they include serum urea, serum creatinine, albuminuria and estimated glomerular filtration rate. Despite all the renal function tests performed indicating association between kidney function and HCV, the only test that has an entire proof of renal dysfunction originating from HCV is cryoglobulin test but also tests that were performed may provide clues about the association between HCV and renal dysfunction considering other factors. The prevalence of renal dysfunction among HCV positive patients on treatment attending Butare university teaching hospital was 28.89%. 

6.2. RECOMMENDATION

To the patients: Because of the high prevalence of renal dysfunction in the HCV positive patient attending Butare university teaching hospital, we recommend that patient with hepatitis C must be screened for serum urea, serum creatinine, albuminuria and EGFR to manage the kidney function on HCV positive patients.

To the ministry of health: Due to the frequency of HCV, high urea, high creatinine, albuminuria is more prevalent at the same time, we recommend that ministry of health must help the patients with HCV to come up with effective intervention, control and treatment strategies for the complications of HCV on kidney function

To the other researchers: we recommend further studies using a large samples size across Rwanda on the assessment of renal function among HCV positive patient and also perform further test such as haematuria, cryoglobulins, complement levels and rheumatoid factor to get enough panel of test.

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