Progression of Kidney Damage in Balkan Endemic Nephropathy: A 15-Year Follow-Up of Patients with Kidney Biopsy Examination

Progression of kidney damage was studied in 18 patients with Balkan endemic nephropathy (BEN), with a mean 15-year follow-up after renal biopsy. According to kidney function, estimated by ^99mTc-DTPA clearance, patients were divided into three groups: with apparently normal kidney function (clearance 103.5 ± 21.3 mL/min/1.73 m²), with incipient renal failure (clearance 65.5 ± 11.3), and with advanced renal failure (clearance 28.0 ± 6.2). The mean yearly decrease of glomerular filtration rate was 2.74 mL/min. In two patients, an increase of kidney function was recorded. Six patients become dialysis dependent, two from the group with incipient renal failure, but all four from the group with advanced renal failure. Three patients died after 8 to 12 years of follow-up, one from causes unrelated to kidney disease and two from end-stage renal failure. This study has shown that BEN is characterized by a slow course and prolonged evolution, modified by medical supervision and treatment.     

Creatinine clearance and kidney size in Balkan endemic nephropathy patients

BACKGROUND/AIMS: Symmetrically shrunken kidneys have been considered as one of the characteristics of Balkan endemic nephropathy (BEN), but there is no agreement when the shrinking does occur in the course of the disease. In the present study, the relation between creatinine clearance (Ccr) and kidney length was compared between the patients in the early phase of BEN and other renal diseases. METHODS: The study included 84 patients with BEN (39 males, aged 54 +/- 12 years), 31 patients with other renal diseases (15 males, aged 54 +/- 14 years) and 15 healthy subjects as controls. Only the patients with Ccr above 90 ml/min were included into the study. The kidney length was measured by sonography using sector sound of 3.5 MHz. RESULTS: In healthy controls and patients with renal disease other than BEN, Ccr varied between 90 and 177 ml/min, and only 3 patients had Ccr above 150 ml/min. On the contrary, 15 (18%) BEN patients had Ccr between 90 and 120 ml/min, and 37 (44%) BEN patients had Ccr above 150 ml/min. Sonographically measured kidney length of all healthy subjects and patients with renal diseases other than BEN was above 10.5 cm. Out of 84 BEN patients, 21 (25%) patients had kidney length less than 10.5 cm. CONCLUSION: BEN patients in the early phase of the disease had significantly higher Ccr and smaller kidney in comparison to the patients with other renal diseases.     

One hundred percent patient and kidney allograft survival with simultaneous liver and kidney transplantation in infants with primary hyperoxaluria: a single-center experience

BACKGROUND: Combined liver-kidney transplantation is the definitive treatment for end-stage renal disease caused by primary hyperoxaluria type I (PH1). The infantile form is characterized by renal failure early in life, advanced systemic oxalosis, and a formidable mortality rate. Although others have reported on overall results of transplantation for PH1 covering a wide age spectrum, none has specifically addressed the high-risk infantile form of the disease. METHODS: Six infants with PH1 underwent simultaneous liver-kidney transplantation at our center between May 1994 and August 1998. Diagnosis was made at 5.2+/-3.3 months of age, they were on dialysis for 11.8+/-2.3 months, and they underwent transplantation at 14.8+/-3.0 months of age when they weighed 10.6+/-1.7 kg. RESULTS: At a mean follow-up of 6.4+/-1.7 years (range, 3.9-8.1 years), we report 100% patient and kidney allograft survival. There were no cases of acute tubular necrosis. Long-term kidney allograft function remained stable in all patients, with serum creatinine values of less than 1.1 mg/dL and a mean creatinine clearance of 99 mL/min/1.73 m2 at follow-up. Those who received combined hemodialysis and peritoneal dialysis pretransplant had lower posttransplant urinary oxalate values than those receiving peritoneal dialysis alone. There was improvement in growth and psychomotor and mental developmental scores after transplantation. CONCLUSIONS: Combined liver-kidney transplantation for the infantile presentation of PH1 is associated with excellent outcome when the approach includes early diagnosis and early combined transplantation, aggressive pretransplant dialysis, and avoidance of posttransplant renal dysfunction.     

Cyst decompression surgery for autosomal dominant polycystic kidney disease.

A prospective study was undertaken to evaluate the efficacy of surgical cyst decompression for retarding the progression of renal failure and for the management of chronic pain associated with autosomal dominant polycystic kidney disease (ADPKD). Thirty patients with ADPKD and pain (14 patients), renal insufficiency (4 patients), or both (12 patients) underwent unilateral (19 patients) or bilateral (11 patients) cyst reduction surgery. The patients were monitored for 21 +/- 2 months postoperatively. The probability of being painfree was 80% at 1 yr and 62% at 2 yr. Preoperative and 1-to 3-month postoperative serum creatinine levels and GFR (clearance of insulin or (125I) iothalamate) were not significantly different (2.2 +/- 0.3 versus 2.2 +/- 0.3 mg/dL and 49 +/- 8 versus 54 +/- 9 mL/min/1.73 m2, respectively). One-year serum creatinine levels remained unchanged in patients with normal preoperative renal function (1.0 +/- 0.07 versus 1.0 +/- 0.05 mg/dL), whereas those with preoperative progressive renal insufficiency had no difference in the mean slope of reciprocal serum creatinine plots preceding and after surgery (-0.008 +/- 0.001 versus -0.009 +/- 0.002 dL/mg/month). In patients who underwent unilateral surgery, split function isotope scans showed no change in function of the operated kidney when compared with the nonoperated kidney. Surgical cyst decompression provides effective relief of chronic pain without compromising renal function. However, the data in this article do not support the use of this procedure to slow progression of renal insufficiency in ADPKD.     

Renal and systemic oxygen consumption in patients with normal and abnormal renal function.

Systemic and renal oxygen consumption and hemodynamics were studied in patients with normal renal function (NI; serum creatinine concentration (Screat), 1.0 +/- 0.04 mg/dL) and those with moderate chronic renal failure with diabetes mellitus Screat, 2.7 +/- 0.2 mg/dL) or without diabetes mellitus (Screat, 2.4 +/- 0.1 mg/dL). Patients with chronic renal failure were anemic and had normal systemic oxygen consumption (NI, 10,564 +/- 277; chronic renal failure, 9,669 +/- 362 mumol of O2/min) and elevated systemic oxygen extraction (NI, 22.9 +/- 1; chronic renal failure, 30.9 +/- 1.2%) (P less than 0.02). Cardiac output and index and arterial oxygen saturation were equivalent in normal patients and in patients with chronic renal failure. Patients with chronic renal failure had higher renal oxygen extraction (NI, 7.3 +/- 0.8; chronic renal failure, 13.9 +/- 1%), lower RBF (NI, 572 +/- 146; chronic renal failure, 197 +/- 20 mL/min/kidney), and lower renal oxygen consumption per kidney (NI, 391 +/- 101; chronic renal failure, 177 +/- 20 mumol of O2/min/kidney) than did normal patients (P less than 0.02). There was a linear relationship between hemoglobin and RBF (r = 0.47, P less than 0.02). Patients with chronic renal failure and diabetes had lower RBF (diabetes mellitus, 146 +/- 23; without diabetes, 242 +/- 28 mL/min/kidney) and renal oxygen consumption per kidney (diabetes mellitus, 131 +/- 21; without diabetes, 218 +/- 29 mumol of O2/min/kidney (P less than 0.03) but equivalent renal oxygen extraction when compared with patients without diabetes. Patients with chronic renal failure without diabetes mellitus had higher renal oxygen consumption when expressed per 100 mL of creatinine clearance (diabetes mellitus, 1,016 +/- 150; without diabetes mellitus, 1,453 +/- 175 mumol of O2/min/100 mL of creatinine clearance; P less than 0.03). There was a significant linear relationship (P less than 0.005, r = 0.38) between calculated creatinine clearance and renal oxygen consumption with a y intercept representing basal renal oxygen consumption (115 mumol of O2/min/kidney) and a slope of 2.3 mumol of O2/mL. Patients with moderate chronic renal failure have normal systemic oxygen consumption but reduced RBF and renal oxygen consumption. The latter parameters are even lower in patients with chronic renal failure and diabetes. Renal hypermetabolism is more likely to exist in nondiabetic than diabetic renal disease. Basic human renal physiology and pathophysiology are described by the relationships between renal oxygen consumption, blood flow, oxygen extraction, and creatinine clearance in patients with normal and abnormal renal function of varied cause.     

No effect of enalapril on progression in autosomal dominant polycystic kidney disease.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors are capable of reducing proteinuria and microalbuminuria with preservation of renal function in diabetic and non-diabetic renal disease. We designed a study investigating the effect of enalapril on the protection of renal function in autosomal dominant polycystic kidney disease (ADPKD). METHODS: We studied 61 normotensive and 28 hypertensive ADPKD patients. The normotensive group participated in a randomized double-blind placebo-controlled study, using enalapril. The hypertensive group was randomized for open label treatment with enalapril or the beta-blocker atenolol. The follow-up was 3 years, and renal function was established repetitively by measuring the clearance of inulin. RESULTS: In the normotensive group, renal function at baseline was 112 +/- 3 ml/min and decreased by -8 +/- 2 ml/min (P < 0.001). The loss of renal function in the patients treated with enalapril or placebo was similar (-7 +/- 3 vs -9 +/- 1 ml/min; P = 0.4). Although blood pressure significantly decreased with enalapril treatment, it had no effect on microalbuminuria. In the hypertensive group, renal function at baseline was 89 +/- 2 ml/min. The mean decline in renal function was -12 +/- 2 ml/min (P < 0.001), and was equal in patients treated with enalapril and those treated with atenolol. The patients treated with atenolol required more additional treatment to control blood pressure, but no difference on microalbuminuria was observed between the two treatments. CONCLUSION: This study was unable to detect a beneficial effect of ACE inhibition on loss of renal function in ADPKD patients.     

Autosomal recessive polycystic kidney disease in adulthood.

BACKGROUND: Renal cysts arising from collecting ducts, congenital hepatic fibrosis, and recessive inheritance characterize autosomal recessive polycystic kidney disease (ARPKD). The disorder usually manifests in infancy, with a high mortality rate in the first year of life. For the patients who survive the neonatal period, the probability of being alive at 15 years of age ranges from 50 to 80%, with 56--67% of them not requiring renal replacement therapy at that stage. Some develop portal hypertension. Long-term outcome of adults escaping renal insufficiency above age 18 is largely unknown. METHOD: In consecutive patients with ARPKD and autonomous renal function at age 18, clinical course of kidney and liver disease in adulthood and status at last follow-up were evaluated. Progression of renal insufficiency was assessed by the rate of decline of creatinine clearance, according to Schwartz's formula before age 18 and Cockcroft and Gault formula thereafter. Severity of liver involvement was estimated by imaging techniques, liver function tests, and endoscopy. RESULTS: Sixteen patients from 15 families were included. ARPKD was diagnosed between 1 day and 13 years of age. From diagnosis, mean follow-up period lasted 24+/-9 years. Before age 18, nine patients (56%) were hypertensive, nine (56%) had renal failure, and four (25%) had portal hypertension. Beyond age 18, no additional patient became hypertensive, and another five developed progressive renal insufficiency; altogether, the mean yearly decline of creatinine clearance was 2.9+/-1.6 ml/min. Portal hypertension was recognized in two additional patients. Four patients experienced gastro-oesophageal bleeding, while recurrent cholangitis or cholangiocarcinoma developed in one case each. At the end of follow-up, 15/16 patients (94%) were alive at a mean age of 27 (18--55) years. Two patients had a normal renal function, 11 had chronic renal insufficiency, one was on regular dialysis, and two had functioning kidney grafts. Four patients had required a porto-systemic shunt. CONCLUSIONS: A subset of ARPKD patients with autonomous renal function at age 18 experiences slowly progressive renal insufficiency. With prolonged renal survival, complications related to portal hypertension are not rare, requiring careful surveillance and appropriate management.     

A single center experience in preemptive kidney transplantation

Transplantation is recognized as preemptive if it takes place before the initiation of chronic dialysis. This maneuver has the potential to avoid the morbidity and burden of chronic dialysis. From November 2003 to April 2005, 15 (7 male, 8 female) end-stage renal failure patients of mean age 40 +/- 14.8 years received preemptive grafts from 2 living-related and 13 cadaveric donors, constituting 11.5% of all kidney transplantations performed in our center at that time. The period on the waiting list for preemptive recipients, namely, 2 weeks to 6 months (mean, 2.4 months), was significantly shorter than that of other patients (mean, 13.8 months). The mean creatinine clearance calculated from the Cockroft Gault formula and the mean plasma creatinine level in preemptive recipients before transplantation were 12.7 +/- 3.1 mL/min and 6.6 +/- 0.8 mg/dL, respectively. The donors for preemptive and non-preemptive groups of recipients did not differ significantly in respect to age, gender, and renal function. The mean number of mismatches of 3.73 and 3.25 and the mean total ischemic times of 9.53 +/- 5 and 11.2 +/- 5 hours, in preemptive and non-preemptive groups of recipients, respectively. The incidence of delayed graft function (dialysis in the first week after transplantation) was significantly lower among preemptive recipients (20% versus 42%, respectively). The groups did not differ either in respect to the occurrence of acute rejection episodes or graft and patient survivals. In preemptive patients the mean plasma creatinine levels at 3 and 12 months were 1.37 +/- 0.3 and 1.09 +/- 0.3 mg/dL, and in non-preemptive patients 1.7 +/- 0.5 and 1.4 +/- 0.4 mg/dL. In conclusion, these results are promising, confirming the notion that preemptive kidney transplantation is the optimal treatment for end-stage renal disease patients.     

Successful Simultaneous Islet-Kidney Transplantation using a Steroid-free Immunosuppression: Two-Year Follow-up

We report on the feasibility of a glucocorticoid-free immunosuppression (sirolimus, low-dose tacrolimus, and daclizumab) in simultaneous islet-kidney transplantation in nine patients with type 1 diabetes. There was one renal primary nonfunction. Renal function (n = 8) as assessed by creatinine and creatinine clearance over time was 103 +/- 6 micromol/L and 64 +/- 6 mL/min/1.73 m(2), respectively. Five out of six patients with >or= 2 islet transplantations became insulin independent. The mean HbA(1c) during the follow-up period for all patients after transplantation is 6.2 +/- 0.9% as compared with 8.7 +/- 1.9% prior to transplant. These results in patients with a median follow-up of 2.3 years suggest that kidney transplantation under a glucocorticoid-free immunosuppression is feasible, and that the rate of insulin independence of 80% can be achieved not only in patients with no or minimal diabetes complications, but also in patients with more advanced late complications and in conjunction with kidney transplantation.     

Living kidney donor follow-up in a dedicated clinic

BACKGROUND: Long-term effects of uninephrectomy for kidney donation are of particular interest in the currently increasing practice of living-donor transplantation. We have retrospectively analyzed the general health status and renal and cardiovascular consequences of living-related kidney donation. METHODS: Data of living-related kidney donors who were regularly followed up in a dedicated clinic at the Sindh Institute of Urology and Transplantation between July 2000 and January 2004 was retrieved. They had donated their kidneys from 1986 onward. Data on weight, blood pressure, creatinine clearance, level of proteinuria, and new onset diabetes mellitus were analyzed. RESULTS: Seven hundred and thirty-six donors with a mean age of 36+/-10.9 years (M:F 1.1:1) were evaluated. With a mean postnephrectomy duration of 3+/-3.2 years (range 6 months-18 years), the creatinine clearance fell to 87% of prenephrectomy values, and 49 (6.7%) had a creatinine clearance of less than 60 mL/ min. Hypertension developed in 76 (10.3%) donors, and 179 (24.3%) had proteinuria exceeding 150 mg/24 hr. Overweight (27.8%) and obese subjects (11.5%) had a higher prevalence of hypertension and new onset diabetes mellitus. One donor developed end-stage renal failure. CONCLUSION: Donor nephrectomy has minimal adverse effects on overall health status. Regular donor follow-up identifies at-risk populations and potentially modifiable factors.     

Effect of pregnancy on long-term function of renal allografts.

Pregnancy in renal allograft recipients is associated with hyperfiltration with the potential for glomerular damage and adverse effects on long-term graft prognosis. We have undertaken a case-controlled study of posttransplant follow-up for a mean of 12 years (range, 4 to 23) in 36 female renal allograft recipients, 18 who became pregnant and 18 controls (matched to underlying disease and renal function) who did not. Assessments included plasma creatinine (PCr), glomerular filtration rate (GFR) by infusion clearance of inulin (Cin), mean arterial pressure (MAP), and documentation of antihypertensive therapy. By the end of follow-up, PCr in the pregnancy group (112 +/- 73 mumol/L [1.26 +/- 0.83 mg/dL]) and controls (127 +/- 52 mumol/L [1.44 +/- 0.59 mg/dL]) had increased by 19% and 8%, respectively, and GFR in the pregnancy group (58 +/- 29 mL/min) and controls (56 +/- 32 mL/min) had decreased by 18% and 7%, respectively. Graft loss or chronic rejection occurred in two patients in each group and there was a death in the pregnancy group 9 years after the second of two successful pregnancies. MAP in the pregnancy group (96 +/- 12 mm Hg) had decreased by 1%, and in the controls (101 +/- 9 mm Hg) had increased by 5%. Two patients in the index group and three in the control group commenced antihypertensive therapy during follow-up. There was, therefore, no evidence of an adverse effect of pregnancy in renal allograft recipients on long-term renal function or development of hypertension.     

The predictive value of 131I-hippurate clearance in the prognosis of acute renal failure

The aim of this investigation was to study the validity of the radionuclide methods in the estimation of kidney function, for prognosis and follow-up of acute renal failure (ARF). In thirty-one ARF patients, the evaluation of glomerular filtration rate (GFR) by 99mTc-DTPA clearance and effective renal plasma flow (ERPF) by 131 I-ortoiodohippurate (131I-OIH) clearance was performed within 7 days and after 6 months from ARF onset. All patients were divided in three groups according to 131I-OIH clearance values obtained within 7 days: group 1, under 150 mL/min; group 2, 150-250 mL/min; and group 3, over 250 mL/min. Seven days clearance values of both radiopharmaceuticals were found to be very low, however, GFR was found more severely impaired than ERPF. Clearance values obtained after 6 months demonstrated no recovery of renal function in the first group, partial recovery in the second and almost complete recovery in the third group. Patients with the lowest 131I-OIH clearance values at the ARF onset had no recovery of renal function, while in the other two groups recovery corresponded to initial 131I-OIH clearance values. In patients with ARF both, 99mTc-DTPA and 131I-OIH clearances were shown suitable for the follow up of renal function, however, only 131I-OIH clearance had a strong predictive prognostic value for renal function recovery in ARF.     

Preemptive kidney transplant from deceased donors: an advantage in relation to reduced waiting list

BACKGROUND: Preemptive living donor kidney transplantation is associated with better allograft and recipient survival. However, it remains unclear whether preemptive transplantation from deceased donors is beneficial too. An increased number of deceased donors has reduced the waiting list in our hospital in the last years allowing preemptive deceased donor kidney transplantation (PDDKT). AIM: We compared our experience with preemptive transplantation with patients who underwent dialysis before transplantation. PATIENTS AND METHODS: Thirty-three PDDKT, including 77.5% male patients of overall mean age of 48 +/- 14 years, were performed in our hospital between January 1999 and December 2004 (8% of transplantations). We compared the outcomes of these patients with those of renal transplants in subjects who had undergone dialysis. The donors for both groups had similar characteristic; they were paired donor kidneys in most cases. RESULTS: The types of donors in both groups were: non-heart-beating (49%), heart-beating deceased (27%) or en bloc pediatric (24%). The serum creatinine of the recipients was 6.9 +/- 1.8 mg/dL prior to transplantation, and the creatinine clearance was 14.6 +/- 3.6 mL/min (estimated by the Cockroft-Gault formula). The Charlson comorbidity index adapted for patients with advanced chronic kidney disease (ACKD) was 0.8 +/- 0.2 in the preemptive group versus 1.7 +/- 0.4 in the dialysis group (P < .05). Delayed graft function rates were 0% versus 25% in preemptive vs dialysis groups, respectively. No differences in 1-month or 1-year renal function as determined by serum creatinine were observed between the groups. We did not observe differences in the incidence of acute rejection or 1- and 2-year graft and patient survivals. CONCLUSION: PDDKT is the treatment of choice for ACKD. It is associated with less delayed graft function and similar 2-year graft and patient survivals than kidney transplantation after dialysis. The Charlson index reflected less comorbidity among patients with PDDKT, a finding that must influence long-term outcomes.     

Clinical outcome of long-term renal transplant survivors: a nephrourologic approach

BACKGROUND: Long-term renal transplant survivors display high incidences of hypogonadism, neoplasms, erectile dysfunction, and metabolic syndrome. Although the urologist has a major role in the kidney transplantation surgery and treatment of the graft-related surgical complications, the follow-up of these patients is essentially focused on kidney function and the immunosuppressive regimen. We sought to evaluate the role of a nephrourologic follow-up for kidney transplant recipients. METHODS: We evaluated 27 male patients of mean age of 48.1 +/- 7.5 years and mean renal allograft follow-up of 12.3 +/- 4.3 years. The nephrourologic approach consisted of evaluation of the urinary system, prostate cancer screening, and assessment of voiding function, fertility, erectile dysfunction, hypogonadism, and metabolic syndrome. We also assessed quality of life. RESULTS: Major urologic findings were found in 18 (66.7%) patients. Four patients reported posttransplantation parenthood. The mean serum creatinine was 1.5 +/- 0.6 mg/dL and the calculated clearance, 72.6 +/- 27.4 mL/min/1.73 m(2). Regarding the voiding pattern, 92.6% of patients showed mild to moderate bladder outlet obstruction. Clinically significant increases in prostate volume were observed in 3.7% of patients. Mean serum total prostate-specific antigen was 1.6 +/- 1.5 ng/mL. Erectile dysfunction was displayed by 46.2% and hypogonadism by 74.1% of patients. Metabolic syndrome was diagnosed in 44.4% of patients, and quality of life was generally rated as good (4/5). CONCLUSION: Long-term renal transplantation survivors show high prevalences of treatable urologic diseases. Thus, we strongly recommend routine complete nephrourologic follow-up of this population.     

The role of comprehensive renal clinic in chronic kidney disease stabilization and management: The Northwestern experience

In this article, we maintain that the management of patients with chronic kidney disease (CKD) is best provided in a clinic setting that integrates nephrologic expertise, patient education, and comprehensive supportive services. Our experience with a CKD clinic in an urban academic setting is described. As a way to assess and quantify the impact of our clinic on clinical outcomes, we have analyzed our results in terms of 2 variables: presence of permanent access at the time of dialysis initiation and impact on renal function as assessed by calculated glomerular filtration rate (GFR). The number of clinic visits was taken as an index of comprehensive renal care before dialysis initiation. Individuals who started dialysis with a functioning permanent access had been seen in our clinic more frequently than those seen less frequently (20 +/- 3.5 and 4.4 +/- 2.1 visits, respectively, P <.005). The impact on renal function was analyzed in a group of 80 unselected patients stratified into 3 stages based on the recently published National Kidney Foundation Disease Outcomes Quality Initiative (K/DOQI) guidelines: stage III (mean GFR 39 +/- 1.5 mL/min, n = 21), stage IV (mean GFR 21 +/- 0.6 mL/min, n = 46), and stage V (mean GFR 12 +/-.76 mL/min, n = 13). Provision of comprehensive renal care in conjunction with anemia management using weekly injections of erythropoietin subcutaneously resulted in stabilization of GFR in patients with stages IV and V over a period of 15 months of follow-up evaluation. In patients with stage III CKD, GFR decreased over the initial period of follow-up evaluation (first few months), and to a lesser extent by the end of follow-up evaluation (15 mo). Further studies are underway to discern the factor(s) underlying the overall clinic effect versus a beneficial effect of anemia correction on GFR. Our data suggests that stabilization of GFR is a goal that can be accomplished with comprehensive renal care provided in an organized clinic setting.     

Long-term beneficial effects of angiotensin-converting enzyme inhibition in patients with nephrotic proteinuria.

Angiotensin-converting enzyme inhibitors (ACEI) can reduce proteinuria in diabetic and nondiabetic nephropathy. However, no studies have determined whether this antiproteinuric effect modifies the progression of renal insufficiency. We studied the evolution of 46 nondiabetic patients with nephrotic proteinuria treated with captopril for a minimum of 12 months. The follow-up period before captopril treatment was 12 to 18 months. At the end of follow-up, after captopril introduction (24.4 +/- 7.6 months), proteinuria had decreased from 6.3 +/- 2.5 to 3.9 +/- 3.1 g/24 h (P less than 0.001), with a mean decrease of 45% +/- 28%. The proteinuria decrease was higher in patients with reflux nephropathy, proteinuria associated with reduction of renal mass, inactive crescentic glomerulonephritis, nephroangiosclerosis, and IgA nephropathy, whereas patients with membranous glomerulonephritis and idiopathic focal glomerulosclerosis showed a poorer response. Patients were separated according to a proteinuria reduction greater (group A, 23 patients) or lower (group B, 23 patients) than 45% of the initial value. At the end of follow-up, renal function had not significantly changed in group A with respect to values at the start of treatment: serum creatinine (SCr) was 229 +/- 167 mumol/L (2.6 +/- 1.9 mg/dL) versus 203 +/- 97 mumol/L (2.3 +/- 1.1 mg/dL), and creatinine clearance (CrCl) was 0.80 +/- 0.52 mL/s (48 +/- 31 mL/min) versus 0.87 +/- 0.47 mL/s (52 +/- 28 mL/min). The slope of the reciprocal of Scr (1/SCr) showed a significantly beneficial change after captopril introduction.(ABSTRACT TRUNCATED AT 250 WORDS)     

The plasma creatinine concentration is not an accurate reflection of the glomerular filtration rate in stable renal transplant patients receiving cyclosporine

We studied 31 stable renal cadaver kidney transplant patients receiving cyclosporine (CyA) and prednisone for immunosuppression to determine what reduction in true glomerular filtration rate (GFR) was reflected by their mild elevation in plasma creatinine concentration (1.8 +/- 0.11 mg/dL). We measured both the creatinine clearance (60 +/- 4.32 mL/min/1.73 m2) and the true GFR using Technetium 99m-DTPA (44 +/- 2.72 mL/min/1.73 m2). The creatinine clearance overestimated true GRF by a mean of 38%, indicating that this percentage of creatinine reached the urine by tubular secretion rather than glomerular filtration. A similar degree of overestimation was found in a separate group of 14 patients receiving imuran for immunosuppression. In 23 patients receiving CyA in whom the serum creatinine concentration was less than 2.0 mg/dL, the mean DTPA clearance was 49.5 +/- 2.83 mL/min/1.73 m2. In stable renal transplant patients receiving CyA, a serum creatinine concentration at, or close to, the upper limit of the normal range may reflect markedly impaired renal function.     

Sequential quadruple immunosuppression including sirolimus in extended criteria and nonheartbeating donor kidney transplantation

The aim was to evaluate feasibility and safety of calcineurin inhibitor-free immunosuppression in high-risk donor kidney transplantation with sequential sirolimus introduction. Kidney transplant patients (n=76) with a donor aged >60 years, donor with acute renal failure, or a nonheartbeating donor were included. Immunosuppression consisted of antithymocyte globulin or basiliximab, mycophenolate mofetil, prednisone, and sequential introduction of sirolimus. One-year patient survival was 96.2% and 95.8%; graft survival was 94.2% and 91.7%; acute rejection rates were 21.2% and 12.4%; delayed graft function was 21.2% and 66.7%; and creatinine clearance was 58+/-20 mL/min and 56+/-21 mL/min for the brain-dead donor group and the nonheartbeating donor group, respectively. Most adverse events were infections, but also three lymphoceles, three urinary fistulas, three wound seromas. Sequential sirolimus introduction in high-risk donor kidney transplantation was found to lead to good patient and graft survival and incidence of acute rejection and delayed graft function.     

Evaluation of kidney function in renal transplant patients receiving long-term cyclosporine

We prospectively assessed renal function in a group of 29 renal transplant patients receiving cyclosporine (CsA) in order to determine the course of their renal function over time and the relationship between different markers of glomerular function. We measured serum creatinine, DPTA, and creatinine clearances, and urinary albumin excretion. The clinical course of 24 patients (83%) permitted repeat studies over a period of 32 +/- 1 (SEM) months, and in these patients DTPA clearance, creatinine clearance, and the serum creatinine concentration did not vary with time. Five of the patients (17%) lost their grafts and returned to dialysis. On initial evaluation patients who lost their grafts had a lower DPTA clearance than those whose function was maintained (29 +/- 3 v 46 +/- 2 mL/min/1.73 m2 body surface area [BSA], respectively, P less than 0.005) and all of them had a DTPA clearance of less than 40 mL/min/1.73 m2 BSA. There was an inverse correlation between the log of the urinary albumin excretion and the DTPA clearance (n = 33, r = -0.59, P less than 0.001), a direct correlation with the serum creatinine concentration (N = 33, r = 0.89, P less than 0.0001), but no correlation with time after transplantation. Thus, despite the continued use of CsA, renal function over time was stable in patients who underwent repeated studies, as was the relationship between the DTPA clearance and the clinically used markers of transplant function, the serum creatinine concentration, and the creatinine clearance.     

Pharmacokinetics and pharmacodynamics of doxacurium in normal patients and in those with hepatic or renal failure.

We determined the pharmacokinetics and duration of action of a bolus dose of doxacurium (15 micrograms/kg) in 27 patients anesthetized with isoflurane and nitrous oxide. Nine patients had normal renal and liver functions and were undergoing a variety of surgical procedures, nine were undergoing cadaveric kidney transplantation because of end-stage renal disease, and nine were undergoing cadaveric liver transplantation because of end-stage hepatocellular disease. Plasma concentrations of doxacurium were measured for 6 h after administration using a sensitive and specific capillary gas chromatographic assay. Plasma concentration versus time data were analyzed by a noncompartmental method based on statistical moments. Neuromuscular blockade was assessed by measuring the electromyographic evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve. The degree of neuromuscular blockade after doxacurium administration was described as the percent of control of the first train-of-four response. The pharmacokinetic variables were (normal vs hepatic failure vs renal failure, respectively): volume of distribution at steady state (220 +/- 110 vs 290 +/- 60 vs 270 +/- 130 mL/kg [mean +/- SD]), plasma clearance (2.7 +/- 1.6 vs 2.3 +/- 0.4 vs 1.2 +/- 0.7 mL.kg-1.min-1), mean residence time (95.2 +/- 57 vs 129.4 +/- 30 vs 270 +/- 210 min), and elimination half-life (99 +/- 54 vs 115 +/- 31 vs 221 +/- 156 min). Plasma clearance and mean residence time differed significantly between patients with renal failure and control patients.(ABSTRACT TRUNCATED AT 250 WORDS)