Mariana S. Markell

Diabetes mellitus after renal transplantation: as deleterious as non-transplant-associated diabetes?

BACKGROUND Despite use of lower doses of corticosteroid hormones after renal allotransplantation in the era of cyclosporine and tacrolimus, posttransplant diabetes mellitus remains a common clinical problem. METHODS We prospectively investigated the effect of posttransplant diabetes on long-term (mean follow-up, 9.3+/-1.5 years) graft and patient survival in the 11.8% of our renal transplant population (n = 40) who developed diabetes after kidney transplantation, and we compared outcome in 38 randomly chosen nondiabetic control patients who had received transplants concurrently. RESULTS Twelve-year graft survival in diabetic patients was 48%, compared with 70% in control patients (P = 0.04), and Coxs regression analysis revealed diabetes to be a significant predictor of graft loss (P = 0.04, relative risk = 3.72) independent of age, sex, and race. Renal function at 5 years as assessed by serum creatinine level was inferior in diabetic patients compared to control patients (2.9+/-2.6 vs. 2.0+/-0.07 mg/dl, P = 0.05). Two diabetic patient who experienced graft loss had a clinical course and histological features consistent with diabetic nephropathy; other diabetes-related morbidity in patients with posttransplant diabetes included ketoacidosis, hyperosmolar coma or precoma, and sensorimotor peripheral neuropathy. Patient survival at 12 years was similar in diabetic and control patients (71% vs. 74%). CONCLUSIONS Posttransplant diabetes mellitus is associated with impaired long-term renal allograft survival and function, complications similar to those in non-transplant-associated diabetes may occur in posttransplant diabetes, and, hence, as in non-transplant-associated diabetes, tight glycemic control may also be warranted in patients with posttransplant diabetes.

Guidelines for the treatment and management of new-onset diabetes after transplantation.

Abstract:  Although graft and patient survival after solid organ transplantation have improved markedly in recent years, transplant recipients continue to experience an increased prevalence of cardiovascular disease (CVD) compared with the general population. A number of factors are known to impact on the increased risk of CVD in this population, including hypertension, dyslipidemia and diabetes mellitus. Of these factors, new‐onset diabetes after transplantation has been identified as one of the most important, being associated with reduced graft function and patient survival, and increased risk of graft loss. In 2003, International Consensus Guidelines on New‐onset Diabetes after Transplantation were published, which aimed to establish a precise definition and diagnosis of the condition and recommend management strategies to reduce its occurrence and impact. These updated 2004 guidelines, developed in consultation with the International Diabetes Federation (IDF), extend the recommendations of the previous guidelines and encompass new‐onset diabetes after kidney, liver and heart transplantation. It is hoped that adoption of these management approaches pre‐ and post‐transplant will reduce individuals’ risk of developing new‐onset diabetes after transplantation as well as ameliorating the long‐term impact of this serious complication.

The effect of kidney size on cadaveric renal allograft outcome

Chronic rejection is the commonest cause of long-term renal allograft loss. Though immunologic factors are thought dominant in its pathogenesis, nonimmunologic factors, in particular, hyperfiltration damage related to reduced renal mass, have also been proposed as factors in the causation of chronic allograft rejection. We assessed the influence of renal size on graft survival and function in all cyclosporine-treated cadaver donor adult renal allograft recipients engrafted at a single center between June 1989 and July 1994, whose grafts functioned for > or = to 3 months (n=169). Patients were divided into 4 groups based on the ratio of kidney volume to recipient body surface area (volume/BSA) (ml/m2), and outcome in groups compared by methods including Coxs proportional hazards and Kaplan-Meier analysis. No significant differences between groups existed for serum creatinine levels, presence of significant proteinuria, or 1- and 5-year graft survival. There was no correlation between volume/BSA and either serum creatinine or degree of proteinuria at 3, 6, 12, 36, and 60 months posttransplant. Volume/BSA was similar in patients with good or poor renal function (58 +/-21 vs. 56 +/- 28 ml/m2), with or without significant proteinuria (57 +/- 24 vs. 60 +/- 25 ml/m2) or in patients who lost their grafts to chronic rejection compared with those with stable allograft function (64 +/- 34 vs. 59 +/- 24 ml/m2). Volume/BSA was not a predictor of graft survival on multivariate regression. We conclude that donor kidney size has no apparent effect on cadaveric renal allograft outcome in the short and intermediate-term, suggesting that close matching of donor kidney size to recipient size is not presently indicated.

Clinical Studies with the Nova Ise for IMg2

The Nova ISE for IMg2+ was utilized to examine IMg2+ in plasma and serum of patients with a variety of pathophysiologic and disease syndromes (e.g., long-term renal transplants [LTRT], during and before cardiac surgery, migraine headaches, head trauma, pregnancy, chronic fatigue syndrome [CFS], non-insulin dependent diabetes mellitus [NIDDM], asthma and after excessive dietary intake of Mg). The results indicate that LTRT treated with cyclosporin A, migraine, head trauma, pregnancy, NIDDM, diseased pregnant, and asthmatic patients all on the average, exhibit significant depression in IMg2+ but not total Mg (TMg). Patients with CFS failed to exhibit changes in serum IMg2+ or TMg levels. Increased dietary load of Mg, for only 6 days, resulted in significant elevations of serum IMg2+ but not TMg. Correlations between the clinical course of several of these syndromes and the fall in IMg2+ were found. The Ca2+/Mg2+ ratio appears to be an important guide for signs of peripheral vasoconstriction and or spasm and possibly enhanced atherogenesis. Overall, the data point to important uses for ISEs for IMg2+ in the diagnosis and treatment of disease states.

Deficiency of serum ionized magnesium in patients receiving hemodialysis or peritoneal dialysis

Serum total magnesium (TMg) measurements in dialysis patients are variable, with some groups reporting hypermagnesemia and some hypomagnesemia. It had not been possible to measure the biologically active fraction, ionized magnesium (IMg2+). The authors utilized an ion-selective electrode to measure IMg in 26 hemodialysis patients and 10 peritoneal dialysis (CAPD) patients and compared the results with those from 66 age matched control subjects. Dialysate magnesium was 0.375 mM/L for the hemodialysis and 0.25 mM/L for the CAPD patients. When compared with control subjects, both hemodialysis and CAPD patients had significantly lower IMg2+ (0.55 +/- 0.02 and 0.50 +/- 0.02 vs. 0.60 +/- 0.004 mM/L; p < 0.05) and greater or normal TMg values (0.99 +/- 0.04, different at the p < 0.001 level, and 0.85 +/- 0.04 vs. 0.84 +/- 0.008). Ionized calcium (ICa2+) values were similar for all three groups (1.15 +/- 0.02 and 1.21 +/- 0.04 vs. 1.17 +/- 0.01), resulting in increased mean ICa2+/IMg2+ ratios (2.14 +/- 0.07 and 2.42 +/- 0.06 vs. 1.95 +/- 0.02 for the control subjects; p < 0.05). The percent of total magnesium that was ionized (%IMg2+) was low in both the hemodialysis and CAPD patients (55.6 +/- 0.93 and 59.2 +/- 1.05) compared with that of control subjects (72 +/- 0.61; p < 0.05). IMg2+ values correlated with TMg values in both hemodialysis (r = 0.93; p < 0.0001) and CAPD (r = 0.92; p < 0.0001) patients did not correlate with age, time on dialysis, weight, fasting cholesterol or triglyceride, albumin, blood urea nitrogen (BUN), creatinine, hematocrit, phosphate, or PTH values.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Early Hyperlipidemia on Graft and Patient Survival in Cyclosporine-Treated Renal Transplant Patients

Hyperlipidemia commonly occurs following renal transplantation. As hyperlipidemia has been postulated to contribute to renal dysfunction in animal models, the effect of early hyperlipidemia was studied in a cohort of 43 cyclosporine-treated renal transplant recipients over a 4-year follow-up period. Hypercholesterolemia occurred in 25 patients, with 18 patients remaining normolipidemic during the initial 3 months following transplantation. Prospective follow-up over a 4-year period was available for 16 of the 18 normolipidemic patients and 25 patients who developed hyperlipidemia, as well as 11 other hyperlipidemic patients who were not included in the initial analysis. Graft function was maintained in 11 (69%) of the patients with early normolipidemia and there has been one patient death (7%). Of the hypercholesterolemic group, two patients were lost to follow-up and 23 of the remaining 34 (68%) had persistent graft function. There have been two patient deaths (6%). No deaths from cardiovascular deaths have occurred in either group, all deaths resulting from infection/sepsis. Mean cholesterol values at 4-year follow-up were 202.0 +/- 11.2 mg/dL for the patients with early normolipidemia 282.9 +/- 14.3 mg/dL for the patients with early hyperlipidemia (p < 0.00001). The most recent cholesterol value was not associated with pretransplant cholesterol value, creatinine, or cyclosporine dose, but was associated with cholesterol value at 3 months both by regression analysis (P < 0.0001) and by Pearson R (r = 0.71, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Vascular access surgery for maintenance hemodialysis. Variables in hospital stay.

Access surgery in support of maintenance hemodialysis is a major factor contributing to prolonged hospitalization in the hemodialysis patient population. In surveying 140 consecutive patients admitted for access surgery, average length of stay was 14 days, independent of race or underlying cause of renal disease. Extended length of stay was most commonly encountered in older patients admitted for thrombosed fistulae or grafts. Postoperative fever, the need for repeated femoral catheterization, delay in access revision or placement due to infection, and the need for adequate social service support resulted in prolonged hospitalization. Understanding and preventing factors that prolong hospitalization may allow the minimization of length of stay in the future and improve quality of life for the end-stage renal disease patient, while also decreasing the cost of care.

Outcome of twin pregnancy in a renal transplant recipient treated with tacrolimus.

Our report describes the outcome of a twin pregnancy in a woman who was maintained on tacrolimus after a living related renal transplant. Both babies born at 32 weeks of gestation developed severe respiratory distress requiring ventilator assistance and went on to develop congestive heart failure. Echocardiograms on both babies showed dilated heart chambers. Twin A succumbed to complications, but twin B, who was treated more aggressively with vasopressors, recovered. Autopsy findings on twin A revealed a thrombotic cardiomyopathy with degeneration of cardiac muscle. We believe that the unusual outcome in this set of twins may have been a result of cardiomyopathy secondary to tacrolimus used by the mother during her pregnancy.

Unrecognized Pseudohyperkalemia as a Cause of Elevated Potassium in Patients with Renal Disease

Pseudohyperkalemia, defined as serum to plasma potassium difference of more than 0.4 mmol/l, occurs when platelets, leukocytes or erythrocytes release intracellular potassium in vitro, leading to falsely elevated serum values. Pseudohyperkalemia has been observed in myeloproliferative disorders [1], including leukemia [2] and infectious mononucleosis [3] as well as in rheumatoid arthritis [4]. We present 2 patients with renal disease and thrombocytosis in whom pseudohyperkalemia was recognized only after common therapeutic measures and/or dialysis failed to effect a decrease in serum potassium. In patients with renal disease and thrombocytosis, plasma as well as serum potassium should be routinely measured prior to instituting aggressive therapy or altering dialysis prescription in order to avoid potentially dangerous overtreatment with resulting hypokalemia.

Erythrocytosis after renal transplantation. A prospective analysis.

A prospective analysis of all cyclosporine treated renal transplants performed between 1987 and 1990 was performed to determine the incidence and etiologic factors of post transplant erythrocytosis (PTE) and its effect on shortterm outcome. PTE developed in 25 (8.1%) recipients (mean age, 41 ± 10 years). PTE occurred more frequently in men (12.8%) than women (1.6%) (p<0.001), diabetic patients (22.9%) than nondiabetic patients (6.2%) (p < 0.001), and rejection-free recipients (11%) compared with those with early rejection (4%) (p<0.05) but was independent of recipient race and donor source. Sixteen patients in whom PTE subsequently developed had pretransplant hematocrits above 30%. PTE occurred most frequently in the first year posttransplant (range, 2-29 months). Serum erythropoietin levels were inappropriately elevated in all patients (mean, 24 ± 2.2 mil/ml), but serum iron, folate, and B12 levels were all normal. Mean serum creatinine and creatinine clearance were 1.7 ± 0.5 mg/dl and 58 ± 20 ml/min, respectively. Twenty-three patients underwent phlebotomy (mean, 3.5 ± 0.5 units) and six had PTE-related complications. In 14 patients, PTE persisted with hematocrit of 53 ± 1.5% (range, 51-56) compared with 57 ± 2.6% (range, 54-64) at the time of PTE onset. In conclusion, PTE occurs primarily in the first year posttransplant and is characterized by inappropriate elevation of erythropoietin. Predictors for PTE include male gender, diabetes mellitus, pretransplant hematocrit above 30%, absence of rejection, and excellent renal allograft function