Hassan N. Ibrahim

Long-term consequences of kidney donation.

BACKGROUND The long-term renal consequences of kidney donation by a living donor are attracting increased appropriate interest. The overall evidence suggests that living kidney donors have survival similar to that of nondonors and that their risk of end-stage renal disease (ESRD) is not increased. Previous studies have included relatively small numbers of donors and a brief follow-up period. METHODS We ascertained the vital status and lifetime risk of ESRD in 3698 kidney donors who donated kidneys during the period from 1963 through 2007; from 2003 through 2007, we also measured the glomerular filtration rate (GFR) and urinary albumin excretion and assessed the prevalence of hypertension, general health status, and quality of life in 255 donors. RESULTS The survival of kidney donors was similar to that of controls who were matched for age, sex, and race or ethnic group. ESRD developed in 11 donors, a rate of 180 cases per million persons per year, as compared with a rate of 268 per million per year in the general population. At a mean (+/-SD) of 12.2+/-9.2 years after donation, 85.5% of the subgroup of 255 donors had a GFR of 60 ml per minute per 1.73 m(2) of body-surface area or higher, 32.1% had hypertension, and 12.7% had albuminuria. Older age and higher body-mass index, but not a longer time since donation, were associated with both a GFR that was lower than 60 ml per minute per 1.73 m(2) and hypertension. A longer time since donation, however, was independently associated with albuminuria. Most donors had quality-of-life scores that were better than population norms, and the prevalence of coexisting conditions was similar to that among controls from the National Health and Nutrition Examination Survey (NHANES) who were matched for age, sex, race or ethnic group, and body-mass index. CONCLUSIONS Survival and the risk of ESRD in carefully screened kidney donors appear to be similar to those in the general population. Most donors who were studied had a preserved GFR, normal albumin excretion, and an excellent quality of life.

Prednisone-Free Maintenance Immunosuppression—A 5-Year Experience

Concern persists that prednisone‐free maintenance immunosuppression in kidney transplant recipients will be associated with an increase in late allograft dysfunction and graft loss. We herein report 5‐year follow‐up of a trial of prednisone‐free maintenance immunosuppression. From October 1, 1999, through January 31, 2005, at our center, 589 kidney transplant recipients were treated with a protocol incorporating discontinuation of their prednisone on postoperative day 6. At 5 years, actuarial patient survival was 91%; graft survival, 84%; death‐censored graft survival, 92%; acute rejection‐free graft survival, 84% and chronic rejection‐free graft survival, 87%. The mean serum creatinine level (±SD) at 1 year was 1.6 ± 0.6; at 5 years, 1.7 ± 0.8. In all, 86% of kidney recipients with functioning grafts remain prednisone‐free as of April 30, 2005.

Weight loss and proteinuria: systematic review of clinical trials and comparative cohorts

BACKGROUND Obesity is a risk factor for the progression of chronic kidney disease (CKD). The impact of weight loss on proteinuria and renal function is less clear. We aimed to determine the effect of intentional weight loss on proteinuria and kidney function. METHODS Three bibliographic databases including Medline, Cochrane and SCUPOS as well as reference list of articles were searched. We included randomized and non-randomized controlled trials as well as single-arm trials published in English through May 2009 which examined urinary protein among obese or overweight adults before and after weight loss interventions including dietary restriction, exercise, anti-obesity medications and bariatric surgery. Study characteristics and methodological quality of trials were assessed. RESULTS Five hundred twenty-two subjects from five controlled and eight uncontrolled trials were included. Weight loss interventions were associated with decreased proteinuria and microalbuminuria by 1.7 g [95% confidence interval (95% CI), 0.7 to 2.6 g] and 14 mg (95% CI, 11 to 17 mg), respectively (P < 0.05). Meta-regression showed that, independent of decline in mean arterial pressure, each 1 kg weight loss was associated with 110 mg (95% CI, 60 to 160 mg, P < 0.001) decrease in proteinuria and 1.1 mg (95% CI, 0.5 to 2.4 mg, P = 0.011) decrease in microalbuminuria, respectively. The decrease was observed across different designs and methods of weight loss. Only bariatric surgery resulted in a significant decrease in creatinine clearance. CONCLUSIONS Weight loss is associated with decreased proteinuria and microalbuminuria. There were no data evaluating the durability of this decrease or the effect of weight loss on CKD progression.

An alternative formula to the Cockcroft-Gault and the modification of diet in renal diseases formulas in predicting GFR in individuals with type 1 diabetes.

Chronic kidney disease is currently on the rise and not only leads to ESRD necessitating dialysis or transplantation but also increases cardiovascular disease risk. Measurement of the GFR, the gold standard for assessing kidney function, is expensive and cumbersome. Several prediction formulas that are based on serum creatinine are currently used to estimate the GFR, but none has been validated in a large cohort of individuals with diabetes. The performance of two commonly used formulas, the abbreviated Modification of Diet in Renal Disease (MDRD) study formula for the GFR and the Cockcroft-Gault estimate of creatinine clearance, were examined against GFR measured by the renal clearance of iothalamate in 1286 individuals with type 1 diabetes from the Diabetes Control and Complications Trial (DCCT). The performance of these formulas was assessed by computing bias, precision, and accuracy. The DCCT participants had normal serum creatinine, unlike the MDRD patients, and somewhat lower creatinine excretion than subjects in the original cohort Cockcroft Gault, which led to biased and highly variable estimates of GFR when these formulas were applied to the DCCT subjects. The MDRD substantially underestimated iothalamate GFR, whereas the Cockcroft Gault formula underestimated it when it was <120 ml/min per 1.73 m(2) and overestimated it when iothalamate GFR was >130 ml/min per 1.73 m(2). Overall, only one third of the formulas estimates were within +/-10% of iothalamate GFR. By underestimating GFR, these formulas were likely to flag early declines in kidney function. Refitting the MDRD formula to the DCCT data gave a more accurate and unbiased prediction of GFR from serum creatinine; percentage of estimate within 10% of measured GFR increased to 56%. A substantial variability in the estimates, however, remained.

Aldosterone in chronic kidney and cardiac disease.

Eberhard Ritz Regulatory systems, which are normally involved in homeostasis, can take on maladaptive roles. This paradoxical situation has been convincingly demonstrated in heart failure. The evidence is strongest with respect to the beneficial effects of sympathetic and renin-angiotensin-

Pregnancy Outcomes After Kidney Donation

The outcome of pregnancy in kidney donors has generally been viewed to be favorable. We determined fetal and maternal outcomes in a large cohort of kidney donors. A total of 2102 women have donated a kidney at our institution; 1589 donors responded to our pregnancy surveys; 1085 reported 3213 pregnancies and 504 reported none. Fetal and maternal outcomes in postdonation pregnancies were comparable to published rates in the general population. Postdonation (vs. predonation) pregnancies were associated with a lower likelihood of full‐term deliveries (73.7% vs. 84.6%, p = 0.0004) and a higher likelihood of fetal loss (19.2% vs. 11.3%, p < 0.0001). Postdonation pregnancies were also associated with a higher risk of gestational diabetes (2.7% vs. 0.7%, p = 0.0001), gestational hypertension (5.7% vs. 0.6%, p < 0.0001), proteinuria (4.3% vs. 1.1%, p < 0.0001) and preeclampsia (5.5% vs. 0.8%, p < 0.0001). Women who had both pre‐ and post‐donation pregnancies were also more likely to have these adverse maternal outcomes in their postdonation pregnancies. In this large survey of previous living donors in a single center, fetal and maternal outcomes and pregnancy outcomes after kidney donation were similar to those reported in the general population, but inferior to predonation pregnancy outcomes.

Calcineurin inhibitor nephrotoxicity: a review and perspective of the evidence.

Background: There is no doubt that acute calcineurin inhibitor (CNI) nephrotoxicity exists; however, chronic CNI nephrotoxicity is questionable at best. Methods: We reviewed the literature to identify original articles related to the use of CNIs in renal and nonrenal solid organ transplantation in order to examine the available evidence about their chronic nephrotoxicity and contribution to graft failure. Results: Early clinical experience and animal studies support the evidence of CNI nephrotoxicity. These findings evolved into the dogma that CNI nephrotoxicity is the major cause of late renal allograft failure. However, in transplanted kidneys the specific role of chronic CNI nephrotoxicity has been questioned. The emerging literature clearly highlights the lack of solid evidence for the role of CNIs as the sole and major injurious agents that cause chronic renal dysfunction and subsequent graft failure. Most of the evidence available to date is against complete CNI avoidance, and minimization appears to be a more viable strategy. It is becoming increasingly clear that the typical pathological lesions linked to chronic CNI use are highly nonspecific, and most of the chronic changes that have been attributed to chronic CNI nephrotoxicity are the consequences of previously unrecognized immunologic injuries. One needs to keep in mind that the potential risk of side effects of CNI use should be balanced against the risk of rejection. Conclusions: More research should focus on addressing the true causes of chronic graft dysfunction rather than focusing on the overexaggerated contribution of CNIs to late graft loss.

Living kidney donor follow-up: State-of-the-art and future directions, conference summary and recommendations

In light of continued uncertainty regarding postkidney donation medical, psychosocial and socioeconomic outcomes for traditional living donors and especially for donors meeting more relaxed acceptance criteria, a meeting was held in September 2010 to (1) review limitations of existing data on outcomes of living kidney donors; (2) assess and define the need for long‐term follow‐up of living kidney donors; (3) identify the potential system requirements, infrastructure and costs of long‐term follow‐up for living kidney donor outcomes in the United States and (4) explore practical options for future development and funding of United States living kidney donor data collection, metrics and endpoints. Conference participants included prior kidney donors, physicians, surgeons, medical ethicists, social scientists, donor coordinators, social workers, independent donor advocates and representatives of payer organizations and the federal government. The findings and recommendations generated at this meeting are presented.

Aldosterone in renal disease.

Blockade of the renin-angiotensin-aldosterone system has proved effective in retarding the progression of renal disease in the remnant kidney model, as well as other experimental diseases, and most importantly, in a range of progressive human renal diseases. Attention has focused on the role of angiotensin II in propagating progression both by its hemodynamic and non-hemodynamic actions. Recent evidence, predominantly in the remnant kidney model, indicates that the drugs used to block this hormone system, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, also lower aldosterone levels. Aldosterone as well as angiotensin II thus appears to be instrumental in sustaining the hypertension and fibroproliferative destruction of the residual kidney.

Prevention of post-transplant cardiovascular disease--report and recommendations of an ad hoc group.

Andrew D. Bostom, Robert S. Brown Jr, Blanche M. Chavers, Thomas M. Coffman, Fernando G. Cosio, Kenneth Culver, John J. Curtis, Gabriel M. Danovitch, Gregory T. Everson, M. Roy First, Cathryn Garvey, Richard Grimm, Marshall I. Hertz, Donald E. Hricik, Lawrence G. Hunsicker, Hassan Ibrahim, Bertram L. Kasiske, Melissa Kennedy, Michael Klag, Mary E. Knatterud, Jon Kobashigawa, John R. Lake, Jimmy A. Light, Arthur J. Matas*, Sue V. McDiarmid, Leslie W. Miller, William D. Payne, Robert Rosenson, David E. R. Sutherland, Amir Tejani, Stephen Textor, Hannah A. Valantine and Russell H. Wiesner