New-onset diabetes after transplant: Incidence, risk factors and outcome.

BACKGROUND: The outcome of renal transplantation depends on achieving effective immunosuppression while minimising the consequences of such treatment. The occurrence of new-onset diabetes in the post-transplant period has been associated with several risk factors including some immunosuppressive medication. Better understanding of the clinical and genetic risk factors associated with new-onset diabetes after transplant (NODAT) could enable risk stratification of patients in the pre-transplant period, with the goal of applying measures that will reduce the incidence. OBJECTIVES: To ascertain the incidence of and clinical and genetic risk factors that predispose to NODAT, and to examine its effect on the outcome of renal transplantation. METHODS: We performed a retrospective cohort review of all renal transplants at Groote Schuur Hospital, Cape Town, South Africa, between 2004 and 2008. Patients who were lost to follow-up or had pre-transplant diabetes or primary non-function were excluded. A subset of the cohort who gave informed consent was enlisted for genetic tests. RESULTS: We identified 111 patients who met the inclusion criteria. The incidence of NODAT was 18.0% (n=20 patients). Risk factors for NODAT included age at transplant (p=0.03), body weight (p=0.04), treatment for acute cellular rejection (p=0.02) and polycystic kidney disease as the cause of renal failure (p=0.005). None of the genes investigated (TCF7L2 rs11196205, rs12255372 and rs7903146 and HNF1ß rs1800575, rs121918671 and rs121918672) was found to be significantly associated with the risk of NODAT. The genotype frequencies for the single-nucleotide polymorphisms studied were closer (although not identical) to those reported for Caucasians than to those reported for the Yoruba (black) population in West Africa. Overall patient survival was 78% at five years, while graft survival was 72%. There was no significant difference in patient or graft survival between the group with NODAT and the group without. CONCLUSIONS: NODAT was common in renal transplant recipients. Some risk factors predate transplant and could be used to risk-stratify patients to determine appropriate risk-reduction strategies. The genetic determinants for NODAT in this population may differ from those reported elsewhere. NODAT had no impact on patient or graft survival in this cohort.

New-onset diabetes after transplant: Incidence, risk factors and outcome

Background. The outcome of renal transplantation depends on achieving effective immunosuppression while minimising the consequences of such treatment. The occurrence of new-onset diabetes in the post-transplant period has been associated with several risk factors including some immunosuppressive medication. Better understanding of the clinical and genetic risk factors associated with new-onset diabetes after transplant (NODAT) could enable risk stratification of patients in the pre-transplant period, with the goal of applying measures that will reduce the incidence.Objectives. To ascertain the incidence of and clinical and genetic risk factors that predispose to NODAT, and to examine its effect on the outcome of renal transplantation.Methods. We performed a retrospective cohort review of all renal transplants at Groote Schuur Hospital, Cape Town, South Africa, between 2004 and 2008. Patients who were lost to follow-up or had pre-transplant diabetes or primary non-function were excluded. A subset of the cohort who gave informed consent was enlisted for genetic tests.Results. We identified 111 patients who met the inclusion criteria. The incidence of NODAT was 18.0% (n=20 patients). Risk factors for NODAT included age at transplant (p=0.03), body weight (p=0.04), treatment for acute cellular rejection (p=0.02) and polycystic kidney disease as the cause of renal failure (p=0.005). None of the genes investigated (TCF7L2 rs11196205, rs12255372 and rs7903146 and HNF1ß rs1800575, rs121918671 and rs121918672) was found to be significantly associated with the risk of NODAT. The genotype frequencies for the single-nucleotide polymorphisms studied were closer (although not identical) to those reported for Caucasians than to those reported for the Yoruba (black) population in West Africa. Overall patient survival was 78% at five years, while graft survival was 72%. There was no significant difference in patient or graft survival between the group with NODAT and the group without.Conclusions. NODAT was common in renal transplant recipients. Some risk factors predate transplant and could be used to risk-stratify patients to determine appropriate risk-reduction strategies. The genetic determinants for NODAT in this population may differ from those reported elsewhere. NODAT had no impact on patient or graft survival in this cohort

Important complications of chronic kidney disease.

The complications of chronic kidney disease (CKD) are dyslipidaemia, hyperkalaemia, metabolic acidosis, anaemia, and bone and mineraldisorders. Dyslipidaemia may be treated with low-density lipoprotein-lowering agents. Statins are ineffective in stages 4 and 5 CKD, but areindicated for preventing the progression of disease in the earlier stages. Chronic acidosis has recently been shown to be a risk factor in theprogression of CKD renal dysfunction. Therefore, treatment is mandatory. Practically, this should consist of 1 - 2 heaped teaspoons of sodiumbicarbonate 2 - 3 times per day, which is an inexpensive and safe therapy that does not raise the blood pressure in spite of the increased sodiumlevel. Target levels of haemoglobin, according to international guidelines, are between 10 g/dL and 12 g/dL. The serum phosphate level is raisedin stage 4 CKD, and especially in stage 5 CKD, which is associated with coronary carotid and other vascular calcifications and may result inischaemic heart disease, myocardial infarction and stroke. A raised parathyroid hormone level (secondary hyperparathyroidism) is also a majorrisk factor for cardiovascular disease and is associated with increased hypertension and resistance to the treatment of CKD-associated anaemia.

Clinicopathological insights into lupus nephritis in South Africans: a study of 251 patients.

There are few published studies on biopsy proven lupus nephritis (LN) from sub-Sahara Africa, mainly due to lack of expertise and pathology back-up for performing and interpreting renal biopsies in many centres. The purpose of this study was to document factors associated with biopsy proven LN and to determine clinical and laboratory models that best predict proliferative LN in South Africans. Of the 251 patients studied, 84.1% were females and 79.3% were of mixed ancestry. There were more observed cases of proliferative LN (63%) than non-proliferative LN. Factors associated with proliferative LN were male gender (p = 0.049), haematuria on dipstix (p < 0.0001), proteinuria on dipstix (p = 0.042), low serum albumin (p = 0.032), low complement C3 (p < 0.0001), low complement C4 (p = 0.009) and positive double-stranded DNA (p = 0.039). Using four models designed from various combinations of the factors associated with proliferative LN, the specificity and positive predictive values were highest for the model that combined gender (male), presence of dipstix haematuria and proteinuria, hypoalbuminaemia, low C3 and low C4 and positive double-stranded DNA (100% respectively). Further study is recommended to identify the value of using these demographic and laboratory parameters in identifying patients with proliferative LN in resource limited centres where the performance of a biopsy is not possible.

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.

Clinical experience with Repotin, a locally produced recombinant human erythropoietin, in the treatment of anaemia of chronic renal failure in South Africa.

OBJECTIVE: To evaluate the efficacy and safety of Repotin, a locally produced recombinant human erythropoietin (rHuEPO), in the treatment of the anaemia of chronic renal failure (ACRF). DESIGN: The study consisted of two multicentre non-randomised open stages. SETTING: Renal units at several teaching hospitals in South Africa. PARTICIPANTS: Haemodialysis patients with haemoglobin (Hb) levels less than 8.0 g/dl were recruited. The first stage examined 26 patients during a 12-week period in which the dose of intravenous rHuEPO was adjusted according to haematological response. In the second stage 27 patients were stabilised with intravenous rHuEPO and then maintained at a Hb level above 8.0 g/dl by subcutaneous administration for up to 1 year. OUTCOME MEASURES: In both stages, outcome was measured by clinical examination, blood pressure, full haematological parameters and blood chemistry. RESULTS: In stage 1, all patients responded to therapy with a statistically significant increase in Hb from geometric means of 6.28 g/dl to 8.50 g/dl (geometric SDs of 1.17 and 1.20 respectively). The doses used ranged from 25 IU to 125 IU/kg (average 47.1). In the second stage, Hb levels reached a mean of 8.06 g/dl (SD 0.9) and were maintained at target range with an average dose of 55.5 IU/kg three times a week. Apart from changes in serum iron, ferritin (associated with increased haematopoiesis) and potassium, there were no significant alterations in blood chemistry. The incidence of adverse events reported during the 12-month second stage was no greater than that reported for other forms of rHuEPO therapy. CONCLUSION: Repotin is a safe and effective rHuEPO preparation for the treatment of ACRF.

Omentopexy for the difficult perigraft lymphocele after renal transplantation.

Between January 1977 and October 1992, 6 patients who had undergone renal transplantation presented with a symptomatic lymphocele that failed to resolve after conventional therapy and eventually required surgical intervention. This complication developed between 7 and 36 months postoperatively. Patients presented with local discomfort combined with deteriorating graft function caused by ureteric obstruction. The lymphoceles recurred after aspiration or external drainage and resolved after omentopexy. We conclude that omentopexy is a satisfactory procedure for the treatment of lymphoceles which fail to resolve after aspiration or external drainage.

Supplemented low-protein diets--are they superior in chronic renal failure?

Twenty-two patients with chronic renal failure were randomly assigned to a conventional low-protein diet containing 0.6 g protein/kg/day or a very-low-protein diet containing 0.4 g protein/kg/day supplemented with essential amino acids; they were followed up for 9 months. There were no significant changes in body mass index, arm muscle area, percentage body fat, serum albumin and transferrin levels in any of the groups; neither was there any difference between the groups in respect of these parameters. Renal function, as measured by the reciprocal of serum creatinine over time, stabilised in both groups during intervention, with no significant difference between the groups. There was however no correlation between changes in renal function and changes in blood pressure, or dietary intake of protein, phosphorus, cholesterol, polyunsaturated and saturated fatty acids. There were also no significant changes and no significant differences between the groups in serum levels of parathyroid hormone and alkaline phosphatase, urine cyclic adenosine monophosphate, tubular reabsorption of phosphate, and the theoretical renal threshold for phosphate. The results of this study suggest that the supplemented very-low-protein diet was not superior to the conventional low-protein diet in terms of its effect on protein-energy status, renal function and biochemical parameters of renal osteodystrophy.

Mycobacterial infection in renal transplant recipients.

STUDY OBJECTIVE: To determine the prevalence and presentation of mycobacterial infection as well as the influence on outcome in graft function and patient survival in renal transplant recipients at our institution. DESIGN: A retrospective review of case records of all renal transplant recipients from 1980 to 1992. SETTING: Groote Schuur Hospital, a large teaching hospital and regional tertiary referral center in Cape Town, South Africa. PATIENTS: During the period reviewed, 857 transplants were performed. The records of 487 patients who had remained in Cape Town were examined. RESULTS: There were 22 cases of mycobacterial infection (21 confirmed or presumed Mycobacterium tuberculosis and 1 unidentified Mycobacterium other than tuberculosis). In seven cases, immunosuppression had been intensified within 3 months of diagnosis. The median time from transplantation to diagnosis was 14 months (range, 2 to 74). Chest radiograph findings included consolidation (14), miliary pattern (4), pleural effusion (3), tuberculoma (2), cavitation (2), and hilar lymphadenopathy (1). Diagnosis of tuberculosis was made on sputum smears (eight), pleural biopsy specimen (two), fine-needle aspiration (one), and fiberoptic bronchoscopy in ten cases (brushings, eight; transbronchial biopsy specimen, three). Extrapulmonary tuberculosis (in addition to pulmonary tuberculosis) occurred in five patients (tuberculous meningitis, one; renal tuberculosis, one; and dissemminated infection, four). Five of the seven patients in whom immunosuppression had been intensified had concurrent infections; two of these died and the remainder returned to dialysis within 6 months. All but one patient received three antituberculosis drugs, including rifampin and isoniazid, for between 6 and 18 months. At the end of the period of review, 12 (59 percent) patients were alive, 10 with functioning grafts and 2 receiving dialysis. Four patients died while receiving antituberculosis treatment, but death was only directly related to tuberculosis in one case. CONCLUSIONS: Tuberculosis is an important infection in renal transplant recipients in Cape Town, but disseminated disease is less common than reported elsewhere.

Which diuretic to use?

The choice of a diuretic depends on knowledge of its efficacy in different disease states as well as the complications associated with its use. However, efficacy of the various diuretic agents as determined in healthy subjects may not always be applicable to the sick patient. The thiazide group appears to be the main offender with regard to hypokalemia and metabolic upsets; these complications seem to stem from long-term use and high dosages. Interest has been expressed on the influence of diuretic induced hypokalemia (and intracellular potassium deficiency) in inducing insulin resistance. The lipid abnormalities may arise as a result of this resistance or may be consequent on hyperinsulinemia from other as yet undetermined mechanisms. In addition, hypertension per se may be associated with insulin resistance. It is interesting to speculate that diuretics, which are commonly used in the treatment of hypertension, may, in some way, perhaps via the induction of hypokalemia, unmask this resistance.

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)

Transplantation for diabetic nephropathy at Groote Schuur Hospital.

Over a period of 6 years, 9 patients with diabetic nephropathy received renal allografts at Groote Schuur Hospital. This low figure represents 2.8% of the total number of renal transplants done at our institution, and is evidence of concern about the apparent poor results of transplantation in these patients. After 2 years, patients and graft survival rates in diabetics were 87% and 62% respectively. Vascular disease was a major problem. Six patients developed limb gangrene, and symptomatic coronary and cerebrovascular disease developed in 2 patients. Infections were common and included wound sepsis, cellulitis, candidiasis and urinary tract infections. Diabetes was poorly controlled after transplantation in 5 patients. Proliferative retinopathy was present in 6 patients but remained stable after transplantation. Despite very strict selection criteria, the results of renal transplantation in diabetic patients remain poor. Better treatment strategies are needed to justify acceptance of these patients for transplantation.

Urinary tissue plasminogen activator in renal disease.

Whereas plasminogen activator of the tissue-type (t-PA) is present in extracts of kidney parenchyma, only small amounts of the enzyme can be detected in normal urine where the major plasminogen activator is of the urokinase-type (u-PA). These observations suggest the existence of physiological or anatomical barriers that effectively confine t-PA to renal tissue and exclude it from the urine. We examined the notion that disease might breach these barriers and so lead to the appearance of abnormal amounts of t-PA in the urine. Under the conditions of the simple fibrinolytic assay that we have developed, urine samples from 30 normal subjects did not contain detectable amounts of t-PA whereas we were able to demonstrate t-PA in samples from 43 of 65 patients with various forms of renal disease. When positive, therefore, tests for the presence of t-PA in human urine provide evidence for renal disease that may not otherwise be apparent.

Renal transplantation in patients with bilateral renal carcinoma--how long should we wait?

Patients with bilateral renal carcinoma or malignancy in a solitary kidney are best managed by radical nephrectomy with subsequent dialysis and transplantation. Because of the risk of recurrence of the tumour, the timing of the transplant procedure is important. We report on two patients with bilateral renal carcinoma who were subjected to radical nephrectomy and then managed with dialysis and transplantation within 6 months.