Diagnosis and management of Pompe disease.

Pompe disease (PD) is an autosomal-recessively inherited neuromuscular disease that, if not diagnosed and treated early, can be fatal. It can present from early infancy into adulthood. Due to the lack of acid alpha-glucosidase, there is progressive intracellular accumulation of glycogen. The severity of the disease is determined by age of onset, organ involvement including the degree of severity of muscle involvement, as well as rate of progression. PD is classified into two groups: infantile and late-onset, each having two subgroups. The need for two tests performed by separate methods (screening and confirmatory) is outlined. It is imperative to try to reduce the time to diagnosis and to recognise the possibilities of false-positive results. A multidisciplinary team approach to treatment of affected patients is optimum with, as team leader, a physician who has experience in managing this rare disorder. In this article, we present a brief overview of the disease and provide guidelines for diagnosis and management of this condition in South Africa.

Is there a need for early detection programs for chronic kidney disease?

The aims of this paper are to examine whether early detection programs are needed to assist in detecting and managing chronic kidney disease (CKD). It draws on existing material which indicates that CKD and its precursor risk factors or illnesses such as hypertension, diabetes mellitus and HIV infection are very clearly major challenges faced by health systems worldwide. This paper evaluates whether CKD meets the epidemiological criteria to justify early screening. More compelling evidence is becoming available which indicates that the prevalence of CKD is significant in both developing and developed countries and that CKD can be easily detected and treated with only small changes to existing practice and this may be improved through screening programs. A brief evaluation of the challenges of establishing early detection programs is provided, as well as an examination of the capacity which exists for establishing such programs. It concludes that, despite the lack of randomized studies, these programs appear to provide an opportunity to integrate CKD management with common chronic illnesses and, through this approach, provide clinical and cost-effective management of both CKD and cardiovascular disease.

Chronic kidney disease in human immunodeficiency virus infection.

The number of people living with human immunodeficiency virus (HIV) worldwide was estimated to be 39.5 million in 2006, 2.6 million more than in 2004. The manifestations of HIV infection in the kidney are multiple and varied, highlighting the complexity of the disease process. There is a wide spectrum of renal disease that occurs in the course of HIV infection. Biopsy studies reveal varying frequencies of histological patterns. HIV-associated nephropathy (HIVAN) is most common. A biopsy study at Chris Baragwanath Hospital in Soweto, South Africa showed that HIVAN was present in 27% and immune complex disease in 21%. Han et al. studied HIV-positive patients in Durban, South Africa and screened for proteinuria, including microalbuminuria. They found persistent proteinuria in 6%; HIVAN in 21/30 (72.4%) and the prevalence of HIVAN in patients with persistent microalbuminuria was 85.7%. Studies in black patients have shown a higher prevalence of both severe glomerular lesions (focal glomerulosclerosis) and nephrotic range proteinuria with renal dysfunction in the presence of normo-hypotension. There have been no prospective randomised controlled studies with any form of therapy for HIVAN to date. Therapy of HIVAN has included corticosteroids, cyclosporine and antiretroviral therapy (ART). ART appears to be a logical choice in the management of HIV-associated renal disease. Regimens containing protease inhibitors have been shown to be associated with significant slowing of the decline in creatinine clearance. Both peritoneal dialysis and haemodialysis are appropriate treatment modalities for HIV-infected patients with end stage renal disease. The choice of dialysis modality between haemodialysis and peritoneal dialysis is not a factor in predicting survival, if patients are stable on ART. Preliminary short-term data in case reports and small cohorts of liver, kidney, and heart transplant recipients suggest that patient survival rates may be similar to those in HIV-uninfected transplant recipients. However, high rates of acute and chronic rejection have been observed among HIV-infected kidney transplant recipients. The Infectious Diseases Society of America (IDSA) published guidelines in 2005, recommending that all individuals be assessed for kidney disease at the time of diagnosis of HIV infection with a screening urinalysis for proteinuria and a calculated estimate of renal function. Therefore any patient with persistent proteinuria, persistent haematuria or glomerular filtration rate < 60 mL/min per 1.73 m(2) should be referred to an institution where a specialist can evaluate this patient for further investigations. An integrated plan to reduce the progression to kidney failure together with lifestyle measures, focusing also on high risk groups with effective management at all levels of chronic kidney disease remains essential.

HIV-related nephropathy: a South African perspective.

Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is an important cause of renal failure in those of African origin. A number of other kidney diseases occur in HIV-positive patients. We conducted a retrospective review of renal biopsies in HIV-positive Black African patients to determine the prevalence of both 'classic HIVAN' and non-HIVAN pathologies in this group. Clinical and laboratory data from HIV-positive patients who underwent renal biopsy from 1st January 2003 to 31st December 2004 were collected. Similar information on HIV-negative patients biopsied during the same period was also recorded by way of comparison to try and assess the influence of the virus on renal histologic patterns. HIV-positive group - 99 biopsies were suitable for study. The main histologic categories were 'classic HIVAN' (27%) and HIV immune complex kidney disease ('HIVICK') (21%). The subepithelial immune deposits in 'HIVICK' induced a newly described 'ball-in-cup' basement membrane reaction. Other glomerulonephritides included membranous, post-infectious disease, mesangial hyperplasia, and immunoglobulin A nephropathy. Overlapping clinical presentations prevented pre-biopsy histologic predictions. HIV-negative group - There were no examples of collapsing focal segmental glomerulosclerosis or nonspecific immune complex disease, but increased numbers of minimal change and membranoproliferative disease. 'Classic HIVAN' accounted for less than a third of the nephropathies occurring in HIV-positive Black South Africans. 'HIVICK' is another important cause of chronic kidney disease in this group. Future research is needed into the earlier detection and treatment of these diseases, which have a high mortality in our context.

Chronic kidney disease management--what can we learn from South African and Australian efforts?

BACKGROUND: The prevalence of chronic kidney disease is on the rise. Our objective is to describe two programs to improve the awareness and management of hypertension, renal disease, and diabetes in remote Australian Aboriginal and urban and periurban South African communities. We focus on how the Australian Aboriginal and South African Chronic Disease Outreach Programs have worked together. METHODS: The establishment of prevention programs in developing countries is a challenge. The paper evaluates these challenges, including accessing international aid. The programs advocate that regular integrated checks for chronic disease and their risk factors are essential elements of regular adult health care. Programs should be run by primary health workers, following algorithms for testing and treatment, and a backup provided by nurse coordinators. Constant evaluation is essential to develop community health profiles and adapt program structure. RESULTS: Both programs are discussed, including how they are organized to deliver preventative and treatment strategies. The challenges and adaptations required are outlined. CONCLUSIONS: It is the aim of the international kidney community to prevent chronic kidney disease. The South African and Australian groups highlight the need for a systematic and sustained approach to the management of chronic diseases to achieve this goal.

The use of a cyclosporin-ketoconazole combination: making renal transplantation affordable in developing countries.

OBJECTIVES: The costs of immunosuppressive drugs in renal transplant recipients remains prohibitively high. Ketoconazole (KZ) has, in limited studies, been shown to significantly reduce the dose of cyclosporin (CyA) after renal transplantation. We report our long-term experience with the use of KZ in a large group of renal transplant recipients. Although this study was not a formal health economic assessment, we undertook a cost-saving analysis of the CyA-KZ combination usage. METHODS: The 170 patients (174 transplants) undergoing renal transplantation between 1991 and 1997 included in the study received CyA (10 mg/kg/day), prednisone (30 mg/day) and azathioprine (100 mg/day) in the immediate perioperative period. At 1 month post-transplantation, KZ (100 mg twice daily) was added and the CyA dose reduced to 25% and the prednisone dose to 50%. The CyA dose was adjusted to maintain trough levels of 150-200 ng/ml. RESULTS: There was an 85% reduction in the dose of CyA. The average costs were 10.61 pounds sterling for CyA alone compared with pound 2.26 (pounds sterling) for the CyA-KZ combination, which represents an average savings of 8.35 pounds sterling (79%) per patient per day. The estimated savings during the study period was 999,930 pounds sterling. The patient and graft survival for patients receiving KZ was similar to patients on the South African Dialysis and Transplant Registry. Graft survival was significantly worse in black patients. CONCLUSION: The use of KZ with CyA in renal transplant recipients with stable allograft function results in a significant reduction in the dose of CyA and a significant cost savings, without compromising patient or graft survival. The regimen may be useful in countries with limited resources.

The role of bone scanning in the detection of metastatic calcification: a case report.

Metastatic calcification associated with renal failure is well described. Bone scanning agents accumulate to various degrees within extraskeletal sites of metastatic calcification. The authors describe a patient with polycystic kidney disease resulting in renal failure, with the subsequent development of secondary hyperparathyroidism and metastatic calcification. Bone scintigraphy revealed abnormal uptake in both lungs, the right leg, and the right hand.