Browsing by Author "Okpechi, Ikechi G"

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    An African perspective on the genetic risk of chronic kidney disease: a systematic review
    (BioMed Central, 2018-10-19) George, Cindy; Yako, Yandiswa Y; Okpechi, Ikechi G; Matsha, Tandi E; Kaze Folefack, Francois J; Kengne, Andre P
    Background Individuals of African ethnicity are disproportionately burdened with chronic kidney disease (CKD). However, despite the genetic link, genetic association studies of CKD in African populations are lacking. Methods We conducted a systematic review to critically evaluate the existing studies on CKD genetic risk inferred by polymorphism(s) amongst African populations in Africa. The study followed the HuGE handbook and PRISMA protocol. We included studies reporting on the association of polymorphism(s) with prevalent CKD, end-stage renaldisease (ESRD) or CKD-associated traits. Given the very few studies investigating the effects of the same single nucleotide polymorphisms (SNPs) on CKD risk, a narrative synthesis of the evidence was conducted. Results A total of 30 polymorphisms in 11 genes were investigated for their association with CKD, ESRD or related traits, all using the candidate-gene approach. Of all the included genes, MYH9, AT1R and MTHFR genes failed to predict CKD or related traits, while variants in the APOL1, apoE, eNOS, XPD, XRCC1, renalase, ADIPOQ, and CCR2 genes were associated with CKD or other related traits. Two SNPs (rs73885319, rs60910145) and haplotypes (G-A-G; G1; G2) of the apolipoprotein L1 (APOL1) gene were studied in more than one population group, with similar association with prevalent CKD observed. The remaining polymorphisms were investigated in single studies. Conclusion According to this systematic review, there is currently insufficient evidence of the specific polymorphisms that poses African populations at an increased risk of CKD. Large-scale genetic studies are warranted to better understand susceptibility polymorphisms, specific to African populations.
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    Baseline predictors of mortality among predominantly rural-dwelling end-stage renal disease patients on chronic dialysis therapies in Limpopo, South Africa
    (Public Library of Science, 2016) Isla, Ramon A Tamayo; Ameh, Oluwatoyin I; Mapiye, Darlington; Swanepoel, Charles R; Bello, Aminu K; Ratsela, Andrew R; Okpechi, Ikechi G
    BACKGROUND: Dialysis therapy for end-stage renal disease (ESRD) continues to be the readily available renal replacement option in developing countries. While the impact of rural/remote dwelling on mortality among dialysis patients in developed countries is known, it remains to be defined in sub-Saharan Africa. METHODS: A single-center database of end-stage renal disease patients on chronic dialysis therapies treated between 2007 and 2014 at the Polokwane Kidney and Dialysis Centre (PKDC) of the Pietersburg Provincial Hospital, Limpopo South Africa, was retrospectively reviewed. All-cause, cardiovascular, and infection-related mortalities were assessed and associated baseline predictors determined. RESULTS: Of the 340 patients reviewed, 52.1% were male, 92.9% were black Africans, 1.8% were positive for the human immunodeficiency virus (HIV), and 87.5% were rural dwellers. The average distance travelled to the dialysis centre was 112.3 ± 73.4 Km while 67.6% of patients lived in formal housing. Estimated glomerular filtration rate (eGFR) at dialysis initiation was 7.1 ± 3.7 mls/min while hemodialysis (HD) was the predominant modality offered (57.1%). Ninety-two (92) deaths were recorded over the duration of follow-up with the majority (34.8%) of deaths arising from infection-related causes. Continuous ambulatory peritoneal dialysis (CAPD) was a significant predictor of all-cause mortality (HR: 1.62, CI: 1.07-2.46) and infection-related mortality (HR: 2.27, CI: 1.13-4.60). On multivariable cox regression, CAPD remained a significant predictor of all-cause mortality (HR: 2.00, CI: 1.29-3.10) while the risk of death among CAPD patients was also significantly modified by diabetes mellitus (DM) status (HR: 4.99, CI: 2.13-11.71). CONCLUSION: CAPD among predominantly rural dwelling patients in the Limpopo province of South Africa is associated with an increased risk of death from all-causes and infection-related causes.
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    Clinico-pathological correlation and outcome in patients with mesangioproliferative glomerulonephritis in Cape Town: A single centre study
    (2018) Barday, Zibya; Okpechi, Ikechi G
    Background Glomerulonephritis is a major cause of end-stage kidney disease (ESRD) in Africa. There is scanty data on the clinico-pathological characteristics and outcome of the mesangioproliferative glomerulonephritides in Africa, despite the non-IgA subtype being reported as a common cause of nephrotic syndrome. This study will assess the outcome of patients with biopsy proven mesangioproliferative glomerulonephritis (MesPGN) from a single centre in Cape Town, South Africa. Methods The study is designed as 10-year retrospective analysis of patients with biopsy proven MesPGN. The MesPGN patterns were divided into non-IgA MesPGN and IgA nephropathy (IgAN), depending on the predominant type of immune deposit. Univariate cox regression analysis was used to determine factors associated with ESRD. Results Data of 109 patients with renal biopsy-proven MesPGN were included for the period between 2005-2014. The mean age at biopsy was 33.8 ±14.9 years, 53.2% were males, and 39.4% were black Africans. Clinically, 58.7% presented with nephrotic syndrome. On histology 79.8% had non-IgA MesPGN, and 20.2% had IgAN. Compared to the non-IgA group, most patients with IgAN were not treated with immunosuppression (72.7% vs. 40.2%; p=0.006). At the last visit, 10.1% reached ESRD (40.9% vs. 2.3%; p<0.0001) and 30.2% achieved complete remission (9.1% vs. 35.7%; p=0.015) for IgAN and non-IgA MesPGN respectively. The 5-year renal survival for IgAN and non-IgA MesPGN respectively, were: 63.3% vs. 97.6%, log rank p=0.001. Overall, hypertension (p=0.019), not receiving immunosuppression (p=0.046) and having IgAN (p=0.007) were independent predictors of progression to ESRD. Conclusion There is a significantly higher ESRD-free survival of patients with biopsy proven non-IgA MesPGN than IgAN. Whether this is related to the limited use of immunosuppressive therapy in IgAN patients or represents a true nature of the disease still requires further research.
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    Clinico-pathological features of repeat renal biopsies in patients with lupus nephritis at Groote Schuur Hospital, Cape Town
    (2017) Kajawo, Shepherd; Okpechi, Ikechi G
    Background: Repeat renal biopsies in patients with lupus nephritis (LN) are usually done to guide treatment or to establish disease chronicity. Their value is not clear from available literature. There is also no available data in Africa to guide clinicians. Methods: This was a retrospective study of patients undergoing a repeat renal biopsy between January 2003 and December 2014 from a single centre in Cape Town, South Africa. Relevant demographic, clinical and histological records of patients with repeat renal biopsies were documented. Comparison of data from 1st and 2nd renal biopsy was performed. Results: 44 patients had at least 2 biopsies done during the study period. Most patients were females (81.8%). The mean biopsy interval was 2.8± 1.8 (range 0.38 – 9.4) years. Proteinuria was the main indication for the repeat biopsy (36.1%). The glomerular filtration rate and proteinuria worsened between the two biopsies (p=0.001 and 0.019) respectively suggesting disease progression. Most patients (65.4%) with a non-proliferative class of LN at first biopsy progressed into a proliferative class whereas patients with initial proliferative LN at first biopsy (77.8%) remained as proliferative at repeat biopsy. Treatment was changed in 85% of patients at second biopsy. Conclusion: Repeat renal biopsies in patients with LN presents a useful means of assessing disease progression and provides guidance regarding modification of treatment. More studies are however required to evaluate the value of repeat biopsies and perhaps the need for protocol renal biopsies in patients with LN.
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    Complications of percutaneous native kidney biopsies in adults in low and middle-income countries: A Systematic review and meta-analysis
    (2021) Kajawo, Shepherd; Okpechi, Ikechi G
    Introduction: Kidney biopsy supports diagnoses, choice of treatment and prognostication in management of kidney diseases. Complications associated with this procedure varies among countries depending on several clinical and technical factors. This Systematic review and meta-analysis aims to report on these complications in low and middle-income countries (LMIC) and compare the burden of complications across different regions. Methods: Two independent reviewers searched studies from 1st January 1980 to 31st December 2017 in PubMed, Cochrane Reviews and African Journals Online. The study-specific estimates were pooled through a random-effects model meta-analysis to obtain an overall summary estimate of major complications across studies. Statistical heterogeneity was evaluated by the Cochrane's Q statistic. Results: 35 studies reporting on 18,456 kidney biopsies met the inclusion criteria. The overall rate of kidney biopsy complications was 14.0% (95% CI 10.0-18.0%).Major complications occurred in 1.3% (95% CI 0.8 – 2.4%) whilst minor complications were 10.9% (95% CI 0.07.4-14.9%). LMIC in Europe and Central Asia had the highest complications 21.4% (95% CI 19.1 – 23.8%) while East Asia and the Pacific had the least rates 7.9% (95% CI 1.8 – 17.7%); p< 0.001. Blind procedures had the highest overall complications, 21.2% (95% CI 17.6 – 25.0%), followed by pre-marking using ultrasound [13.9% (95% CI 7.8-21.3%) and least complications with real-time ultrasound (p=0.003). Death occurring post kidney biopsy was reported in 2 patients. Conclusion: Major complications associated with kidney biopsies in LMIC were low. However, minor complications still occur in significant proportions. Ultrasound-guided kidney biopsies and appropriate training will mitigate some of these risks.
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    Diagnostic performance of glomerular PLA2R and THSD7A antibodies in biopsy confirmed primary membranous nephropathy in South Africans
    (2021-01-07) Lwezaula, Bingileki F; Ameh, Oluwatoyin I; Ekrikpo, Udeme E; Botha, Francois C; Okpechi-Samuel, Ugochi S; Wearne, Nicola; Ronco, Pierre; Bello, Aminu K; Okpechi, Ikechi G
    Background: Serum and tissue-based tests using phospholipase A2 receptor 1 (PLA2R) and thrombospondin type-1 domain containing 7A (THSD7A) are established immune biomarkers for the diagnosis of primary membranous nephropathy (PMN). This study assessed the diagnostic performance of these biomarkers in the diagnosis of PMN in South Africans. Methods This was a cross-sectional analysis from a single centre in Cape Town, South Africa. Relevant biodata was collected from all patients. Histology, including slides for PLA2R and THSD7A were processed and assessed by typical microscopic and immunohistochemical features. Biopsy tissues of patients with membranous lupus nephritis (LN-V) and diabetic nephropathy (DN) were used as controls. The diagnostic accuracy for diagnosis of PMN using positive PLA2R and THSD7A were evaluated. Results Of the 88 patients included, 41 had PMN with a mean age of 44.5 ± 17.5 years and 61.0% were female. Histologically, PLA2R and THSD7A were only positive in the PMN group (51.2% and 4.9%, respectively) but negative in both control groups. The sensitivity of PLA2R and THSD7A for identifying PMN was 51.2% and 4.9%, respectively. The sensitivity of both tests together was 53.7% while the specificity and positive predictive values (PPV) for any of the tests (alone or in combination) was 100%. There was no difference in the sensitivity and specificity when using PLA2R alone compared to combining the two tests (p=0.32). Conclusion Glomerular staining of PLA2R and THSD7A could have potential diagnostic values in South Africans. This has implications on how immunotherapies can be initiated and used in these settings.
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    Epidemiology and clinical outcomes of patients with idiopathic membranous glomerulonephritis at Groote Schuur Hospital over a ten year period
    (2015) Ameh, Oluwatoyin Idaomeh; Okpechi, Ikechi G
    BACKGROUND: Glomerulonephritis is a common cause of end-stage renal disease (ESRD) in developing countries. Idiopathic membranous nephropathy (IMGN) is an identified cause of nephrotic syndrome in South Africa. Early attainment of complete remission (CR) or partial remission (PR) in patients with IMGN has been shown to slow progression to ESRD. There is a dearth of outcome studies in Africa on IMGN. METHODS: This study was approved by the institution's Human Research Ethics Committee. It was a retrospective review of patients diagnosed (biopsy-proven) with IMGN at the Division of Nephrology and Hypertension, Groote Schuur Hospital, Cape Town, over a 10-year period. Secondary causes of MN were excluded in this study. Demographic, clinical, biochemical and histological records of such patients were retrieved for analysis. The trends in clinical and biochemical parameters over the course of follow-up from baseline were also determined. The primary outcome of interest was the attainment of a CR or PR at the last date of follow-up. Predictors of the composite of CR and PR at the last follow-up visit were assessed using univariate and multivariate Cox-Regression analysis. The trend in estimated glomerular filtration rate over the median duration of follow-up was evaluated as a secondary outcome. RESULTS: There were 56 patients with histologic and clinical parameters compatible with the diagnosis of IMGN. There were 26/56 females (46.4%) with an overall mean age of 41.5±14.6 years. Forty-three (43) patients had subsequent follow-up care at our centre with a median duration of follow-up of 23.0 (13.0, 48.0) months. Sixteen patients (37.2%) were treated with immunosuppression (ISP)-combination of steroids and cyclophosphamide, and 81.4% received renin-angiotensin system (RAS) blockade. There were no statistically significant differences in demographic and clinical features of patients treated with or without ISP. Trends in level of proteinuria, estimated GFR and serum albumin concentrations were also not significantly different between the two groups. Eighteen patients (41.9%) reached CR or PR at the last visit. There were also no statistically significant differences in demographic, clinical, histological, and biochemical characteristics of patients who had or had not achieved remission. The median time-to-remission of patients treated with or without ISP was similar - 48.6 and 48.7 months respectively (p=0.13) while the proportions of patients not reaching CR/PR at 1 year and 2 years were 94.6% and 80.8% respectively by Kaplan-Meier analysis. Gender, race and u se of immunosuppression did not influence remission status (log rank p>0.05). On regression analysis, the predictors of CR/PR at last follow up visit were GFR [OR 1.01 (95%CI: 1.00 - 1.02); p=0.041] and systolic BP (OR 0.97 [95%CI: 0.95 – 0.99); p=0.036]. CONCLUSION: Remission outcomes with the current immunosuppressive treatment protocol for I M G N are delayed and poor. There is a need for its re-evaluation and also for longitudinal, multicenter studies to assess the best treatment approach (-es) to IMGN in South Africa.
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    Epidemiology of histologically proven Glomerulonephritis in Africa: A systematic review and meta-analysis
    (Public Library of Science, 2016) Okpechi, Ikechi G; Ameh, Oluwatoyin I; Bello, Aminu K; Ronco, Pierre; Swanepoel, Charles R; Kengne, Andre P
    Background and aim: Glomerulonephritis (GN) is a leading cause of end-stage renal disease (ESRD) in Africa. Data on epidemiology and outcomes of glomerular diseases from Africa is still limited. We conducted a systematic review on the epidemiology of histologically proven glomerular diseases in Africa between 1980 and 2014. Materials and methods We searched literature using PubMed, AfricaWide, the Cumulative Index to Nursing and Allied Health Literature on EBSCO Host, Scopus, African Journals online databases, and the African Index Medicus, for relevant studies. The review was conducted using standard methods and frameworks using only biopsy-confirmed data. RESULTS: Twenty four (24) studies comprising 12,093 reported biopsies from 13 countries were included in this analysis. The median number of biopsies per study was 127.0 (50-4436), most of the studies (70.0%) originated from North Africa and the number of performed kidney biopsies varied from 5.2 to 617 biopsies/year. Nephrotic syndrome was the commonest indication of renal biopsy. The frequency of reported primary pathologic patterns included, minimal change disease (MCD); 16.5% (95%CI: 11.2-22.6), focal segmental glomerulosclerosis (FSGS); 15.9% (11.3-21.1), mesangiocapillary GN (MCGN); 11.8% (9.2-14.6), crescentic GN; 2.0% (0.9-3.5) and IgA nephropathy 2.8% (1.3-4.9). Glomerular diseases related to hepatitis B and systemic lupus erythematosus had the highest prevalence among assessed secondary diseases: 8.4% (2.0-18.4) and 7.7% (4.5-11.7) respectively. There was no evidence of publication bias and regional differences were seen mostly for secondary GNs. CONCLUSIONS: Glomerular diseases remain poorly characterized in sub-Saharan Africa due to declining renal biopsy rates and consequent paucity of data on pathologic patterns of key renal diseases. Development of renal biopsy registries in Africa is likely to enable adequate characterization of the prevalence and patterns of glomerular diseases; this could have a positive impact on chronic kidney disease evaluation and treatment in the African continent since most glomerulopathies are amenable to treatment.
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    Genetic variation at selected SNPs in the leptin gene and association of alleles with markers of kidney disease in a Xhosa population of South Africa
    (Public Library of Science, 2010) Okpechi, Ikechi G; Rayner, Brian L; van der Merwe, Lize; Mayosi, Bongani M; Adeyemo, Adebowale; Tiffin, Nicki; Ramesar, Rajkumar
    BACKGROUND: Chronic kidney disease (CKD) is a significant public health problem that leads to end-stage renal disease (ESRD) with as many as 2 million people predicted to need therapy worldwide by 2010. Obesity is a risk factor for CKD and leptin, the obesity hormone, correlates with body fat mass and markers of renal function. A number of clinical and experimental studies have suggested a link between serum leptin and kidney disease. We hypothesised that variants in the leptin gene ( LEP ) may be associated with markers of CKD in indigenous black Africans. METHODOLOGY/PRINCIPAL FINDINGS: Black South Africans of Xhosa (distinct cultural Bantu-speaking population) descent were recruited for the study and four common polymorphisms of the LEP (rs7799039, rs791620, rs2167270 and STS-U43653 [ENSSNP5824596]) were analysed for genotype and haplotype association with urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), Serum creatinine (Scr) and serum leptin level. In one of the four single nucleotide polymorphisms (SNPs) we examined, an association with the renal phenotypes was observed. Hypertensive subjects with the T allele (CT genotype) of the ENSSNP5824596 SNP had a significantly higher eGFR (p = 0.0141), and significantly lower Scr (p = 0.0137). This was confirmed by haplotype analysis. Also, the haplotype GAAC had a modest effect on urine albumin-to-creatinine ratio in normotensive subjects (p = 0.0482). Conclusions/Significance These results suggest that genetic variations of the LEP may be associated with phenotypes that are markers of CKD in black Africans.
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    Outcome of patients with primary immune-complex type Mesangiocapillary Glomerulonephritis (MCGN) in Cape Town South Africa
    (Public Library of Science, 2014) Okpechi, Ikechi G; Dlamini, Thandiwe A L; Duffield, Maureen; Rayner, Brian L; Moturi, George; Swanepoel, Charles R
    Background and Aim Mesangiocapillary glomerulonephritis (MCGN) is a common cause of chronic kidney disease in developing countries. Data on the renal outcome of patients with idiopathic MCGN is limited. The aim of this study is to investigate the outcome of patients with idiopathic MCGN presenting to the Groote Schuur Hospital (GSH) Renal Unit in Cape Town. Materials and METHODS: A retrospective study of patients with idiopathic MCGN followed up at our clinic. Seventy-nine patients with no identifiable cause of MCGN were included for analysis. A composite renal outcome of persistent doubling of serum creatinine or end stage renal disease (ESRD) was used. Kaplan Meier survival and Cox regression analysis were used to assess survival and identify factors predicting the outcome. RESULTS: The mean age at biopsy was 33.9±13.6 years and 41.8% were black. Mean duration of follow up was 13.5±18.8 months. Twenty-three patients (34.2%) reached the composite endpoint. Overall, median renal survival was 38.7±11.7 months (95% CI 15.7-61.8) with 2-year and 5-year renal survival of 61% and 40.3% respectively. No significant difference was found for renal survival between males and females, treatment or non-treatment with immunosuppression, presence or absence of crescents or histological type of MCGN (p>0.05). On univariate Cox-regression analysis, factors found to be associated with the outcome were the estimated glomerular filtration rate at biopsy (OR 0.97 [95%CI: 0.95-0.99], p<0.0001), black race (OR 3.03 [95%CI: 1.27-7.21], p = 0.012) and presence of interstitial fibrosis in the biopsy (OR 2.64 [95%CI: 1.07-6.48], p = 0.034). Age, systolic blood pressure and attaining complete or partial remission approached significant values with the endpoint. CONCLUSIONS: The outcome of idiopathic MCGN in Cape Town is poor and requires further prospective studies to improve our understanding of this common disease.
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    Outcomes of renal transplantation in patients with lupus nephritis: a single centre study in Cape Town
    (2017) Almradi, Ahmed Khalifa Mohamed; Okpechi, Ikechi G
    Background: Kidney disease (lupus nephritis [LN]) constitutes a feature of systemic lupus erythematosus (SLE) in up to 50 - 70% of patients with the disease. Although most LN patients are suitable for renal transplantation when they develop end stage renal disease (ESRD), the risk of recurrence of LN post-transplantation can be as high as 30%. Since the outcomes of renal transplantation in ESRD-LN patients has not been adequately studied in South Africa, the present study aims to retrospectively explore the aforementioned objective in a single centre. Methodology: The study was designed as a retrospective descriptive study of patients with LN transplanted in the renal unit of Groote Schuur Hospital, Cape Town from 1st January 2004 to 31st December 2013. Results: There were 454 patients who were transplanted in the study period of which 15/454 (3.3%) had LN. The M:F ratio of LN patients was 1:14, mean age was 25±10 years, all were known with class- IV LN and 10/15 (66.7%) received graft from a cadaveric donor. Immunosuppression was initiated in 7/15 (46.7%) with combination of cyclosporine and azathioprine; in 2/15 (13.3%) with tacrolimus and azathioprine and in 6/15 (40.0%) with Tacrolimus and MMF. All patients received corticosteroids. Recurrence of LN was seen in one patient (6.7%) who developed class V LN. Graft rejection was diagnosed in 10/15 cases (66.7%) with types of rejection noted to be acute cellular rejection in 6/15 (40%), antibody mediated rejection 1/15 (6.7%) and chronic rejection in 3/15 (20%). ESRD occurred in 3 patients (20%) with causes from antibody mediated rejection (6.7%), chronic allograft nephropathy (6.7%) and renal artery thrombosis (6.7%). Mean time to ESRD was 16.0 months. Five deaths (33.3%) occurred from sepsis in 3/15 (20%), pulmonary embolism; 1/15 (6.7%) and progressive ESRD after non-acceptance to the chronic dialysis program; 1/15 (6.7%). Mean time to death was 44.1 months. Conclusion: This study shows that recurrence of LN in the graft kidney is uncommon in South Africa. However, effort to reduce high rates of rejection and improve graft and patient survival still needs to be studied.
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    A practical approach to the nutritional management of chronic kidney disease patients in Cape Town, South Africa
    (BioMed Central, 2016-07-08) Ameh, Oluwatoyin I; Cilliers, Lynette; Okpechi, Ikechi G
    Background: The multi-racial and multi-ethnic population of South Africa has significant variation in their nutritional habits with many black South Africans undergoing a nutritional transition to Western type diets. In this review, we describe our practical approaches to the dietary and nutritional management of chronic kidney disease (CKD) patients in Cape Town, South Africa. Discussion: Due to poverty and socio-economic constraints, significant challenges still exist with regard to achieving the nutritional needs and adequate dietary counselling of many CKD patients (pre-dialysis and dialysis) in South Africa. Inadequate workforce to meet the educational and counselling needs of patients, inability of many patients to effectively come to terms with changing body and metabolic needs due to ongoing kidney disease, issues of adherence to fluid and food restrictions as well as adherence to medications and in some cases the inability to obtain adequate daily food supplies make up some of these challenges. A multi-disciplinary approach (dietitians, nurses and nephrologists) of regularly reminding and educating patients on dietary (especially low protein diets) and nutritional needs is practiced. The South African Renal exchange list consisting of groups of food items with the same nutritional content has been developed as a practical tool to be used by dietitians to convert individualized nutritional prescriptions into meal plan to meet the nutritional needs of patients in South Africa. The list is currently utilized in counselling CKD patients and provides varied options for food items within the same group (exchangeable) as well as offering ease for the description of suitable meal portions (sizes) to our patients. Summary: Regular and continuous education of CKD patients by a multi-disciplinary team in South Africa enables our patients to meet their nutritional goals and retard CKD progression. The South African renal exchange list has proved to be a very useful tool in meeting this need.
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    Prevalence of polypharmacy and associated adverse health outcomes in adult patients with chronic kidney disease: protocol for a systematic review and meta-analysis
    (2021-07-04) Okpechi, Ikechi G; Tinwala, Mohammed M; Muneer, Shezel; Zaidi, Deenaz; Ye, Feng; Hamonic, Laura N; Khan, Maryam; Sultana, Naima; Brimble, Scott; Grill, Allan; Klarenbach, Scott; Lindeman, Cliff; Molnar, Amber; Nitsch, Dorothea; Ronksley, Paul; Shojai, Soroush; Soos, Boglarka; Tangri, Navdeep; Thompson, Stephanie; Tuot, Delphine; Drummond, Neil; Mangin, Dee; Bello, Aminu K
    Background Polypharmacy, often defined as the concomitant use of ≥ 5 medications, has been identified as a significant global public health threat. Aging and multimorbidity are key drivers of polypharmacy and have been linked to a broad range of adverse health outcomes and mortality. Patients with chronic kidney disease (CKD) are particularly at high risk of polypharmacy and use of potentially inappropriate medications given the numerous risk factors and complications associated with CKD. The aim of this systematic review will be to assess the prevalence of polypharmacy among adult patients with CKD, and the potential association between polypharmacy and adverse health outcomes within this population. Methods/design We will search empirical databases such as MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science, and PsycINFO and grey literature from inception onwards (with no language restrictions) for observational studies (e.g., cross-sectional or cohort studies) reporting the prevalence of polypharmacy in adult patients with CKD (all stages including dialysis). Two reviewers will independently screen all citations, full-text articles, and extract data. Potential conflicts will be resolved through discussion. The study methodological quality will be appraised using an appropriate tool. The primary outcome will be the prevalence of polypharmacy. Secondary outcomes will include any adverse health outcomes (e.g., worsening kidney function) in association with polypharmacy. If appropriate, we will conduct random effects meta-analysis of observational data to summarize the pooled prevalence of polypharmacy and the associations between polypharmacy and adverse outcomes. Statistical heterogeneity will be estimated using Cochran’s Q and I2 index. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., sex, kidney replacement therapy, multimorbidity). Discussion Given that polypharmacy is a major and a growing public health issue, our findings will highlight the prevalence of polypharmacy, hazards associated with it, and medication thresholds associated with adverse outcomes in patients with CKD. Our study will also draw attention to the prognostic importance of improving medication practices as a key priority area to help minimize the use of inappropriate medications in patients with CKD. Systematic review registration PROSPERO registration number: [ CRD42020206514 ].
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    Standardised Outcomes in Nephrology – Chronic Kidney Disease (SONG-CKD): a protocol for establishing a core outcome set for adults with chronic kidney disease who do not require kidney replacement therapy
    (2021-09-09) Evangelidis, Nicole; Sautenet, Benedicte; Madero, Magdalena; Tong, Allison; Ashuntantang, Gloria; Sanabria, Laura C; de Boer, Ian H; Fung, Samuel; Gallego, Daniel; Levey, Andrew S; Levin, Adeera; Lorca, Eduardo; Okpechi, Ikechi G; Rossignol, Patrick; Sola, Laura; Usherwood, Tim; Wheeler, David C; Cho, Yeoungjee; Howell, Martin; Guha, Chandana; Scholes-Robertson, Nicole; Widders, Katherine; Gonzalez, Andrea M; Teixeira-Pinto, Armando; Viecelli, Andrea K; Bernier-Jean, Amelie; Anumudu, Samaya; Dunn, Louese; Wilkie, Martin; Craig, Jonathan C
    Background Globally, over 1.2 million people die from chronic kidney disease (CKD) every year. Patients with CKD are up to 10 times more likely to die prematurely than progress to kidney failure requiring kidney replacement therapy. The burden of symptoms and impaired quality of life in CKD may be compounded by comorbidities and treatment side effects. However, patient-important outcomes remain inconsistently and infrequently reported in trials in patients with CKD, which can limit evidence-informed decision-making. The Standardised Outcomes in Nephrology – Chronic Kidney Disease (SONG-CKD) aims to establish a consensus-based core outcome set for trials in patients with CKD not yet requiring kidney replacement therapy to ensure outcomes of relevance to patients, caregivers and health professionals are consistently reported in trials. Methods SONG-CKD involves four phases: a systematic review to identify outcomes (domains and measures) that have been reported in randomised controlled trials involving adults with CKD who do not require kidney replacement therapy; stakeholder key informant interviews with health professionals involved in the care of adults with CKD to ascertain their views on establishing core outcomes in CKD; an international two-round online Delphi survey with patients, caregivers, clinicians, researchers, policy makers and industry representatives to obtain consensus on critically important outcome domains; and stakeholder consensus workshops to review and finalise the set of core outcome domains for trials in CKD. Discussion Establishing a core outcome set to be reported in trials in patients with CKD will enhance the relevance, transparency and impact of research to improve the lives of people with CKD. Trial registration Not applicable. This study is registered with the Core Outcome Measures in Effectiveness Trials (COMET) database: http://www.comet-initiative.org/Studies/Details/1653 .
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    The effects of add-on corticosteroids on renal outcomes in patients with biopsy proven HIV associated nephropathy: a single centre study from South Africa
    (BioMed Central, 2019-02-06) Wearne, Nicola; Swanepoel, Charles R; Duffield, Maureen S; Davidson, Bianca J; Manning, Kathryn; Tiffin, Nicki; Boulle, Andrew; Rayner, Brian L; Naidu, Priyanka; Okpechi, Ikechi G
    Background The aim of this study was to assess, the efficacy and safety of add-on corticosteroids to antiretroviral therapy [ART] in patients with biopsy proven HIV associated nephropathy. Methods All included patients had histological evidence of either collapsing or non-collapsing focal segmental glomerulosclerosis (FSGS) or podocyte and/or parietal cell hypertrophy or hyperplasia. All patients had evidence of tubulointerstitial inflammation with microcysts. Patients were randomized to ART with the addition of 1 mg/kg of corticosteroids [ART+C] or remained in the group [ART Alone] and followed for 2 years. A repeat biopsy was performed at 6 months. Results Twenty-one patients were randomized to [ART+C] and 17 to [ART Alone]. The baseline estimated glomerular filtration rate (eGFR) was significantly lower in the [ART+C] vs. [ART Alone] group [35mls/min/1.73m2 vs. 47 mls/min/1.73m2, p = 0.015]. The [ART+C] cohort had a statistically significant improvement in median (eGFR) from baseline to last follow up compared with [ART Alone] i.e. [Δ = 25mls/min (IQR: 15;51) vs 9 mls/min (IQR: 0–24), p = 0.008]. There were no statistically significant differences between the groups when proteinuria and histology were analyzed. There were 8 deaths during the trial period, 7 from [ART+C] (Log rank p = 0.071). Conclusions In the [ART+C] cohort there was a significant improvement in eGFR over 2-years with increased mortality. Routine corticosteroid use cannot currently be recommended. Further investigation to define which subgroup of this cohort would safely benefit from the positive effects is required. Trial registration ISRCTN study ID ( 56112439 ] was retrospectively registered on the 5 September 2018.