Diabetes mellitus as predictor of patient and graft survival after kidney transplantation.

BACKGROUND: In this study, we used a single-center database to examine the risks of renal transplantation in patients with diabetes mellitus (DM). We aimed to compare 1-year outcomes of survival and morbidity after renal transplantation among recipients with and without DM. METHODS: We reviewed retrospectively 1211 adult patients who underwent renal transplantation from January 2001 to December 2010. The patients were divided into 2 groups: Those with (33%) and those without (67%) pretransplant diabetes. Unpaired Student's t tests and χ(2) tests were used to compare outcomes between diabetic and nondiabetic renal transplant recipients. We analyzed survival, renal function, development of proteinuria, rejection, and infection (requiring hospitalization). RESULTS: Patients with diabetes were older, had a greater body mass index (mean, 29.5 vs 25.3 kg/m(2); P < .05), and had lower creatinine clearance (44.2 ± 11.4 vs 56.0 ± 18.2; P = .01). Forty-one patients died in hospital (3.4%; P = nonsignificant). Furthermore, survival rates were similar between these 2 groups. However, we found a trend toward decreased survival for those with DM at 1 year (80.4% vs 88.7%; P = .20). Mean follow-up time was 3.2 years. Infection rate within 6 months was greater among those with DM (19% vs 5%; odds ratio, 6.25). Freedom from rejection at 3 years was similar (75.2% vs 76.8%; P = .57). Multivariate analysis showed increased baseline creatinine level as a significant risk factor for survival. Body mass index >30 kg/m(2) was a significant risk factor for survival among patients with DM. CONCLUSION: We found an increased risk of serious infections in patients with DM, particularly within the first 6 months. However, our data suggest that diabetes is not associated with worse 1-year survival or higher morbidity in renal transplant patients, as long as good blood glucose control is maintained.

Distance from treatment facility and risk of death from cardiovascular and infectious causes in renal transplant patients.

We investigated whether patients receiving RTx who live farther from their attending nephrologist are more likely to die than those who live closer. A random sample of 167 patients who undergone RTx between 1996 and 2004 was examined. We calculated the distance between each patient's residence and the practice location of their attending nephrologist. We used Cox proportional hazards models to examine the adjusted relation between distance and clinical outcomes (death from all causes, rejection episodes, infectious causes, and cardiovascular complications) over a follow-up period of upto 6 years. During the follow-up period (median: 3.3, range: 1.0-6.5 years), 22% of patients died. Compared with patients who lived within 50 km of their nephrologist, the adjusted hazard ratio of death was 1.04 among those who lived 50.1-150 km away, 1.16 for those who lived 150.1-300 km away, and 1.19 for those who lived more than 300 km (P for trend <0.001). The risk of death from infectious causes increased with greater distance from the attending nephrologist (P for trend <0.001). The risk of developing acute rejection episodes did not increase with distance from the attending nephrologist (P for trend = 0.2). The risk of death from cardiovascular causes increased with distance from the attending nephrologist (P for trend <0.05). Compared with patients who lived within 50 km of their nephrologist, the adjusted hazard ratio of death among those who lived >300 km away was 1.75 for infectious causes and 1.39 for cardiovascular causes. We conclude that mortality and morbidity associated with RTx was greater among patients who lived farther from their attending nephrologist, as compared with those who lived closer.

The burden of anti-HCV genotye-4 positivity in renal transplant recipients: 8 years follow-up.

Whether renal transplant recipients with anti-HCV antibodies positivity and normal liver function tests within the first year after transplantation have different morbidity and mortality and graft failure compared to anti-HCV-negative recipients remains controversial. In this retrospective study, on 411 renal transplant recipients, we analyzed grafts morbidity, survival, and liver function tests over a period of 8 years. Patients were stratified according to their anti-HCV antibody status 1 year after transplantation into anti-HCV-positive and HCV-negative patients. The presence of normal liver function tests was mandatory at inclusion. All patients received the same immunosuppressive protocol consisting of cyclosporine A, mycophenolate mofetil and steroids. One year after transplantation, 137 patients were anti-HCV negative (33 %) while the rest 274 (67 %) were positive. At 5 years of follow-up, the study population consisted of 205 patients (71 patients, 35 % with anti-HCV negativity, and 134, 65 % with positivity). At the end of the study, only 144 patients were followed up (43 patients, 30 % with negative anti-HCV and 101 patients, 70 %, with positivity). We found that graft survival was not different between both groups. Moreover, serum creatinine showed a trend to be lower in HCV-positive patients compared to negative group although difference was not statistically significant. The number of graft loss was not different between both groups. Moreover, there was no difference between both groups as regards prevalence of acute rejection, diabetes mellitus, hypertension, CMV disease and proteinuria. We can conclude that anti-HCV positivity for 8 years in patients with normal liver function tests at 1 year does not impact graft morbidity and patient survival.

Sirolimus therapy for patients with adult polycystic kidney disease: a pilot study.

A pilot study was performed on adult polycystic kidney disease (PCKD) patients to examine the effects of the anti-proliferative mammalian target of rapamycin inhibitor sirolimus on the growth of renal cysts. Eight consecutive PCKD patients were given sirolimus (1 mg/d PO) for 6 consecutive months, in addition to an angiotensin receptor blocker (ARB), namely telmisartan. Another 8 PCKD patients served as a control group given only telmisartan. All PCKD patients had a serum creatinine value <2 mg/dL with a negative urine culture before enrollment. All patients were diagnosed by renal magnetic resonance imaging (MRI) to measure renal volumes. After a 6-month follow-up, patients were rescanned to remeasure the MRI volumes. Renal function was stable in 5/8 subjects in the sirolimus group, improved in 2 cases, and worsened in 1 with an increase of serum creatinine to >2 mg/dL resulting in his withdrawal after 5 months of follow-up. In contrast, the serum creatinine value was stable in 3 control group subjects, worsen in 3, and improved in 2. Four patients in the sirolimus group experienced infectious complications, namely, urinary tract infections (UTI) in 2 which were treated with antibiotics, and monilial pharyngitis in 2, who were treated and cured with a topical antifungal. In the control group, only 2 developed and were treated for UTIs. Hematologic tests were normal in all patients. There was an insignificant rise in kidney volume as measured by MRI in the sirolimus group (2845 vs 3221 mL after 6 months; P = NS) compared with a significant increase in the control group (2667 vs 3590 mL after 6 months; P < .05). We concluded that sirolimus, in addition to an ARB, might be beneficial for PCKD patients who present early in their illness.

Possible new role for angiotensin-converting enzyme inhibitors in treating glomerulonephritis.

Serum transforming growth factor-beta (TGF-beta1) production was estimated for 10 patients with essential hypertension, 12 patients with glomerulonephritis (5 hypertensive and 7 normotensive) and 10 healthy controls. The glomerulonephritis group received angiotensin-converting enzyme inhibitor captopril 25-75 mg/day for 4 weeks. Blood urea, serum creatinine, 24-hour urinary protein and serum TGF-beta1 were then re-estimated. Urea and creatinine were significantly higher in the hypertension and glomerulonephritis groups than in the controls and also higher in the glomerulonephritis group than the hypertension group. TGF-beta1 was significantly higher in the glomerulonephritis groups than in the control and hypertension groups. TGF-beta1 and 24-hour urinary protein were significantly reduced in the glomerulonephritis group.

Possible new role for angiotensin-converting enzyme inhibitors in treating glomerulonephritis

Serum transforming growth factor-beta [TGF-beta1] production was estimated for 10 patients with essential hypertension, 12 patients with glomerulonephritis [5 hypertensive and 7 normotensive] and 10 healthy controls. The glomerulonephritis group received angiotensin-converting enzyme inhibitor captopril 25-75 mg/day for 4 weeks. Blood urea, serum creatinine, 24-hour urinary protein and serum TGF-beta1 were then re-estimated. Urea and creatinine were significantly higher in the hypertension and glomerulonephritis groups than in the controls and also higher in the glomerulonephritis group than the hypertension group. TGF-beta1 was significantly higher in the glomerulonephritis groups than in the control and hypertension groups. TGF-beta1 and 24-hour urinary protein were significantly reduced in the glomerulonephritis group

Verapamil corrects abnormalities in norepinephrine metabolism of brain synaptosomes in CRF.

Abnormalities in norepinephrine (NE) metabolism of brain synaptosomes occur in chronic renal failure (CRF), and this has been attributed to the parathyroid hormone (PTH)-induced accumulation of calcium in synaptosomes. The present study examined the effect of treatment with the calcium-channel blocker verapamil on NE content, release, and uptake, on Na(+)-K(+)-ATPase activity, and on calcium content of brain synaptosomes from rats with 21 days of CRF. Verapamil treatment of normal rats for 21 days did not affect synaptosomal NE content, release, or uptake, Na(+)-K(+)-ATPase activity, or calcium content. Rats with 21 days of CRF displayed a significant (P less than 0.01) reduction in their synaptosomal NE content, release, and uptake, an increase in Na(+)-K(+)-ATPase activity, and a significant (P less than 0.01) increase in calcium content of synaptosomes. The treatment of CRF rats with verapamil normalized synaptosomal NE content and release and Na(+)-K(+)-ATPase activity, produced a significant (P less than 0.01) improvement in NE uptake, and prevented the accumulation of calcium in synaptosomes. The data of the present study are consistent with the notion that the abnormalities in synaptosomal NE metabolism and Na(+)-K(+)-ATPase in CRF are mainly the result of PTH-induced accumulation of calcium in synaptosomes and could be prevented by a calcium-channel blocker.

Excess parathyroid hormone adversely affects lipid metabolism in chronic renal failure.

Hyperlipidemia is common in chronic renal failure (CRF), but the underlying mechanisms are not clearly defined. Certain data points toward a potential role for the state of secondary hyperparathyroidism of CRF in its pathogenesis. We examined the effects of parathyroid hormone (PTH) on lipid metabolism utilizing intravenous fat tolerance test (IVFTT) and post-heparin lipolytic activity in five normal dogs, in six animals with CRF and secondary hyperparathyroidism (NPX) and in six normocalcemic-thyroparathyroidectomized dogs (NPX-PTX) with comparable degree and duration of CRF. NPX dogs had fasting hypertriglyceridemia (82 + 6.0 mg/dl vs. 49 +/- 2.7 mg/dl in normal dogs, P less than 0.01), abnormal IVFTT, and reduced post-heparin plasma LPL activity (151 +/- 10 vs. 275 +/- 15 mumol fatty acids/ml/min in normal dogs, P less than 0.01). The NPX-PTX dogs had normal fasting levels of serum triglycerides (42 +/- 0.6 mg/dl), normal IVFTT, and normal post-heparin plasma LPL (317 +/- 19 mumol fatty acids/ml/min) despite CRF. Post-heparin HL activity in plasma was not different between NPX and NPX-TPX dogs. The results show that excess blood levels of PTH and not other consequences of CRF are mainly responsible for the abnormalities in lipid metabolism. The data are consistent with the notion that excess PTH reduces post-heparin LPL activity in plasma, which in turn results in impaired lipid removal from the circulation and consequently hyperlipidemia.

Correction of glucose intolerance and the impaired insulin release of chronic renal failure by verapamil.

Insulin release from pancreatic islets is impaired in chronic renal failure (CRF), and this is due to the state of secondary hyperparathyroidism of CRF. This defect in association with resistance to the peripheral action of insulin-caused glucose intolerance in CRF. It has been suggested that the impaired insulin release induced by excess parathyroid hormone (PTH) is related to the ability of the hormone to augment calcium entry into the pancreatic islets, resulting in accumulation of calcium in the pancreas. Therefore, a calcium channel blocker may antagonize this effect of PTH, and hence normalize glucose tolerance in CRF. The present study examined this postulate by studying intravenous glucose tolerance and insulin release from pancreatic islets in normal and CRF rats and in CRF animals treated with the calcium channel blocker, verapamil. Rats with 42 days of CRF displayed impaired glucose tolerance, significant reduction (P less than 0.01) in insulin release by islets, and doubling of calcium content of the pancreas (P less than 0.01) as compared to normal rats. Simultaneous treatment of CRF rats with verapamil for 42 days resulted in normal glucose tolerance, higher blood insulin levels during glucose infusion, normal calcium content of the pancreas, and normal insulin secretion by the islets. Treatment of normal rats with verapamil for 42 days did not affect any of the parameters studied. The results show that the calcium channel blocker, verapamil, by preventing calcium accumulation in the pancreas, reversed the abnormalities in insulin release that occur in CRF. This effect allowed a greater rise in blood levels of insulin during glucose infusion in CRF rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Parathyroid hormone interferes with extrarenal disposition of potassium in chronic renal failure.

Available data suggest that the permeability of cellular membranes to potassium is affected by cytosolic calcium. Parathyroid hormone (PTH) has a calcium ionophoric property; it enhances calcium entry into many cells and it increases calcium content in a variety of tissues. Therefore, it is possible that clinical states with excess PTH may affect potassium homeostasis. The present study examined the effect of secondary hyperparathyroidism of chronic renal failure (CFR) on extrarenal potassium disposition of intravenous KCl load in rats with CRF. Experiments were performed after 21-26 days of CRF produced by 7/8 nephrectomy in rats with intact parathyroid glands (CRF control), in normocalcemic parathyroidectomized CRF animals (CFR-PTX) and in adrenalectomized CRF rats (CRF-ADX) maintained with DOCA. The effects of treatment with calcium channel blocker, verapamil, and of PTH administration were also examined. The baseline plasma concentrations of potassium in CRF-PTX rats and in CRF control animals treated with verapamil were significantly (p less than 0.01) lower than those with CRF control and CRF-ADX rats. At the end of 90 min of KCl infusion, the plasma concentrations of potassium as well as the changes from baseline were significantly (p less than 0.01) higher in CRF animals with secondary hyperparathyroidism (CRF control and CRF-ADX) and in those treated with PTH (CRF control with PTH and CRF-PTX with PTH) than in those without secondary hyperparathyroidism CRF-PTX and in those with secondary hyperparathyroidism but treated with verapamil (CRF control with verapamil and CRF-ADX with verapamil).(ABSTRACT TRUNCATED AT 250 WORDS)