Charles R. Swanepoel

Morphologic Features of the Myopathy Associated With Chronic Renal Failure

Our previous studies indicate that impaired function of skeletal muscle limits the exercise tolerance of patients with end-stage renal failure who are either maintained on dialysis or undergo renal transplantation. To study the morphology of the condition, muscle biopsies were performed on eight patients with renal failure-associated myopathy. Control samples were taken from seven healthy athletes undergoing knee surgery and from five otherwise healthy but untrained subjects. Tissues were examined by routine light and transmission electron microscopy. Histochemical staining of frozen sections for myosin adenosine triphosphatase and quantitative computer-assisted morphometry of the fiber type and size was performed. The mean (+/- SD) size for type I fibers in patients was 61.2 +/- 11.8 microns, while type II fibers measured 46.7 +/- 11.4 microns. The mean percentage of type II fibers was 67% +/- 12%. These values are within the normal population range and were not different from controls. Significant changes were found on light microscopy of patient samples. These included fiber splitting, internalized nuclei, nuclear knots, moth-eaten fibers, fiber degeneration and regeneration, increased content of lipid droplets, and fiber-type grouping. Electron microscopy showed a large variety of nonspecific abnormalities, including mitochondrial changes, Z-band degeneration, myofilament loss, and accumulation of intracellular glycogen. Ten of 12 control subjects showed no such changes; minor abnormalities were noted on both light and electron microscopy in the remaining two subjects. Muscle oxidative capacity (19.5 +/- 5.1 microL O2/min) for patients with end-stage renal failure was not different from values for those who had undergone renal transplantation, but was lower than values found in trained athletes.(ABSTRACT TRUNCATED AT 250 WORDS)

Isokinetic Muscle Strength Predicts Maximum Exercise Tolerance in Renal Patients on Chronic Hemodialysis

Patients with end-stage renal disease receiving chronic hemodialysis have impaired exercise tolerance. To distinguish between a central cardiorespiratory and a peripheral skeletal muscular origin for this fatigue, we measured exercise performance and peak oxygen consumption during a maximum exercise test in 10 patients receiving chronic hemodialysis. Skeletal muscle function was measured with an isokinetic cycle ergometer and a Cybex II isokinetic dynamometer. Peak rates of oxygen consumption (17.7 +/- 3.6 [mean +/- SD] mL O2/kg/min), blood lactate concentrations (3.4 +/- 0.9 mmol/L), peak heart rates (168 +/- 12 beats/min), and rates of ventilation (37.3 +/- 14.6 L/min) were low, but respiratory exchange ratios (1.1 +/- 0.1) were compatible with maximal effort. There was a significant correlation between isokinetic muscle strength and VO2 peak, exercise duration, peak ventilation, and peak blood lactate concentrations (P less than 0.05 to less than 0.001), but not between hemoglobin concentration, total blood hemoglobin content, or hematocrit and these variables. Therefore, in renal dialysis patients, isokinetic muscle strength is a better predictor of exercise capacity than are variables determining blood oxygen carrying capacity. This suggests that altered skeletal muscle function explains the impaired exercise tolerance of anemic patients with end-stage renal disease receiving chronic hemodialysis.

The spectrum of renal histologies seen in HIV with outcomes, prognostic indicators and clinical correlations

BACKGROUND Two hundred and twenty-one HIV-positive renal biopsies were analysed from Groote Schuur Hospital to determine outcomes and prognostic indicators based on histology and clinical features. METHODS The histology findings were compared with patient demographics, clinical and renal parameters, mortality, CD4 count and date of commencing combined anti-retroviral therapy (cART). Follow-up was between 1 and 3.5 years. RESULTS We found a spectrum of renal histologies in HIV-positive patients of which HIV-associated nephropathy (HIVAN) was the most common histology. cART reduced the mortality in those with any feature of HIVAN by 57% [adjusted hazard ratio (AHR) 0.43, 95% confidence interval (CI) 0.22-0.85]. Of those patients with HIVAN who died, 79% died of renal failure as registered on their death certificate. Proteinuria and microcysts were shown to be poor prognostic indicators (AHR 1.36: 1.09-1.70 and 2.04: 1.24-3.37). In patients with HIVAN alone followed for up to 2 years on cART, estimated glomerular filtration rate remained stable and there was a trend towards decreased proteinuria. cART improved survival in patients with isolated immune complex disease. CONCLUSIONS As mortality is improved in patients with any feature of HIVAN or isolated immune complex disease, cART should be initiated once any of these histological features are established. We believe the spectrum of disease that constitutes HIVAN needs to be more specifically defined. The ultimate outcome may be determined by the histological subtype.

Effect of Rifampicin on Cyclosporin A Blood Levels in a Renal Transplant Recipient

Dr. M.J.D. Cassidy, Departments of Medicine and Surgery, University of Cape Town, Medical School and Groote Schuur Hospital, Cape Town (South Africa) Dear Sir, Rifampicin is a powerful enzyme inducer acting on the cytochrome P 450 enzyme system in the liver and thus may affect the metabolism of a number of drugs [1]. The interaction of rifampicin with glucocorticoids is well recognised and the adverse effect of this combination of drugs on renal allograft function has previously been reported [2]. It has been recommended that renal transplant recipients have their dose of prednisolone increased, by a factor of at least 2, should they be treated concurrently with rifampicin [3]. We report on a renal transplant recipient who developed low whole blood levels of cyclosporin whilst being treated with rifampicin for tuberculosis. A 57-year-old man with Balkan ne-hropathy and end-stage renal failure received a cadaveric renal allograft in March 1984. He had a past history of pulmonary tuberculosis and a grossly abnormal chest radiograph. At the time of surgery he received 250 mg of methylprednisolone intravenously, and immunosup-pression was achieved thereafter with methylprednisolone, 24 mg/day by mouth and cyclosporin A, 4 ml twice daily (13 mg/kg/day) diluted in orange juice. In addition, antituberculous therapy consisting of isoniazid, 300 mg, pyrazinamide 1,500 mg, and rifampicin, 450 mg, daily was commenced. There was immediate graft function following transplantation, the serum creatinine falling to 334 μmol/l (3.8 mg/dl) by day 2 and 165 μmol/l (1.9 mg/dl) by day 20 after transplantation. Whole blood cyclosporin levels (Sandoz Radioimmunoassay) fell progressively and remained low despite an increased dose of cyclosporin. Blood samples were drawn for the trough levels 1 h prior to the administration of the morning dose of cyclosporin and the peak levels were obtained at 4 h following the dose. On the withdrawal of rifampicin, blood levels of cyclosporin rose dramatically (fig. 1). Renal function has remained satisfactory and cycloCyclosporin dose, ml 9 9 8 8 8 8 8 9 10 10 10 10 10 10 10 10 9.5 95 9 9

The acute, the chronic and the news of HIV-related renal disease in Africa.

The burden of renal disease in human immunodeficiency virus (HIV) and AIDS patients living in Africa is adversely influenced by inadequate socio-economic and health care infrastructures. Acute kidney injury in HIV-positive patients, mainly as a result of acute tubular necrosis, may arise from a combination of hemodynamic, immunological, and toxic insult. A variety of histopathological forms of chronic kidney disease is also seen in HIV patients; HIV-associated nephropathy (HIVAN) and immune complex disease may require different treatment strategies, which at present are unknown. The role of host and viral genetics is still to be defined, especially in relation to the different viral clades found in various parts of the world and within Africa. The arrival and availability of highly active antiretroviral therapy in Africa has given impetus to research into the outcome of the renal diseases that are found in those with HIV. It has also generated a new look into policies governing dialysis and transplantation in this group where previously there were none.

Microalbuminuria and the metabolic syndrome in non-diabetic black Africans

It is recognised that the metabolic syndrome promotes the development of cardiovascular disease. Although several studies have shown a relationship between the metabolic syndrome and kidney disease, few of these have used non-diabetic subjects, especially in the African population. This was a cross-sectional study of subjects of African origin, using the metabolic syndrome (MS) criteria of the National Cholesterol Education Program (NCEP) third Adult Treatment Panel (ATP III). Subjects with impaired fasting glucose, with two-hour glucose ≥ 11.1 mmol/L after a glucose tolerance test, were excluded. Spot urine for albuminto-creatinine ratio (ACR) was measured and the glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease (MDRD) equation. Microalbuminuria was defined as ACR between 3–30 mg/mmol. There was a significant decline in GFR and a significant increase in ACR with increasing number of MS traits. ACR increased four-fold between subjects with no MS traits and those with four or more traits. In subjects with the metabolic syndrome, there was a significant correlation between ACR and systolic blood pressure (SBP), diastolic blood pressure (DBP) and fasting glucose. Estimated GFR correlated significantly and inversely with body mass index (BMI) and serum leptin. These observations raise major clinical and public health concerns for developing countries, where both the metabolic syndrome and kidney disease are being reported more and more frequently. The potential economic impact is huge.

Outcome of patients with membranous lupus nephritis in Cape Town South Africa

BACKGROUND The kidney is one of the major target organs affected by systemic lupus erythematosus. Although proliferative forms of lupus nephritis (LN) occur more frequently than membranous LN (MLN), the latter appears to have a more favourable outcome. Only a few studies have reported the outcome of patients with MLN. METHODS A retrospective analysis of patients with biopsy-confirmed MLN from a single centre in South Africa treated from 1st January 2000 to 31st December 2009. RESULTS The mean age of the patients (n = 42) at onset of LN was 35.0 ± 12.8 years with 73.8% of the patients being of mixed ancestry (coloureds). Eleven patients (26.2%) reached the composite end point of death or end-stage renal disease or persistent doubling of serum creatinine. The overall median survival and median renal survival times were 82.3 ± 15.5 months (95% confidence interval 52.0-112.6) and 84.5 ± 15.0 months (55.1-113.8), respectively. Also, 5-year event-free survival and renal survival were 64 and 71%, respectively. On multivariate analysis, systolic blood pressure (BP) during follow-up (P = 0.029), diastolic BP during follow-up (P = 0.020) and attainment of complete remission at 6 months (P = 0.033) were factors associated with the composite end points. Although treatment with chloroquine was not significantly associated with the composite end points (P = 0.05), we found that patients who received chloroquine had better renal survival compared with those who did not (P = 0.007). CONCLUSIONS The outcome of patients with MLN in Cape Town is poorer than for similar patients reported from other centres across the world. Better BP control may significantly influence outcome of disease in these patients.

Understanding kidney care needs and implementation strategies in low- and middle-income countries: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference

Evidence-based cinical practice guidelines improve delivery of uniform care to patients with and at risk of developing kidney disease, thereby reducing disease burden and improving outcomes. These guidelines are not well-integrated into care delivery systems in most low- and middle-income countries (LMICs). The KDIGO Controversies Conference on Implementation Strategies in LMIC reviewed the current state of knowledge in order to define a road map to improve the implementation of guideline-based kidney care in LMICs. An international group of multidisciplinary experts in nephrology, epidemiology, health economics, implementation science, health systems, policy, and research identified key issues related to guideline implementation. The issues examined included the current kidney disease burden in the context of health systems in LMIC, arguments for developing policies to implement guideline-based care, innovations to improve kidney care, and the process of guideline adaptation to suit local needs. This executive summary serves as a resource to guide future work, including a pathway for adapting existing guidelines in different geographical regions.

Acute dialysis in HIV-positive patients in Cape Town, South Africa

Aim:  The prognosis for HIV patients needing acute dialysis is uncertain. The aim of this study was to describe the clinical presentation, renal diagnoses and outcomes of HIV patients who underwent acute haemodialysis at Groote Schuur Hospital in the period 2002–2007.

A renal registry for Africa: first steps

There is a dearth of data on end-stage renal disease (ESRD) in Africa. Several national renal registries have been established but have not been sustainable because of resource limitations. The African Association of Nephrology (AFRAN) and the African Paediatric Nephrology Association (AFPNA) recognize the importance of good registry data and plan to establish an African Renal Registry. This article reviews the elements needed for a successful renal registry and gives an overview of renal registries in developed and developing countries, with the emphasis on Africa. It then discusses the proposed African Renal Registry and the first steps towards its implementation. A registry requires a clear purpose, and agreement on inclusion and exclusion criteria, the dataset and the data dictionary. Ethical issues, data ownership and access, the dissemination of findings and funding must all be considered. Well-documented processes should guide data collection and ensure data quality. The ERA-EDTA Registry is the worlds oldest renal registry. In Africa, registry data have been published mainly by North African countries, starting with Egypt and Tunisia in 1975. However, in recent years no African country has regularly reported national registry data. A shared renal registry would provide participating countries with a reliable technology platform and a common data dictionary to facilitate joint analyses and comparisons. In March 2015, AFRAN organized a registry workshop for African nephrologists and then took the decision to establish, for the first time, an African Renal Registry. In conclusion, African nephrologists have decided to establish a continental renal registry. This initiative could make a substantial impact on the practice of nephrology and the provision of services for adults and children with ESRD in many African countries.