Renal Complications of Hematopoietic Stem Cell Transplantation: Report of a Case and Review of the Literature.

We report the development of minimal change disease superimposed on preexisting chronic kidney disease secondary to chronic calcineurin inhibitor nephrotoxicity in a hematopoietic stem cell transplantation (HSCT) recipient and review the renal complications of HSCT.

Immunosuppression Minimization and Avoidance Protocols: When Less Is Not More.

Kidney transplantation is well established as the best treatment option for end-stage kidney disease. It confers not only a better quality of life but also a significant survival advantage compared to dialysis. However, despite significant improvement in short-term kidney transplant graft survival over the past three decades, long-term graft survival remains suboptimal. Concerns about the possible contribution of chronic calcineurin inhibitor (CNI) nephrotoxicity to late allograft failure and other serious adverse effects of currently used immunosuppressive agents (especially corticosteroids) have led to increasing interest in developing regimens which may better preserve kidney allograft function and minimize other immunosuppression-related problems without increasing the risk of rejection. The availability of newer immunosuppressive agents has provided the opportunity to formulate such regimens. Approaches to this end include minimization, withdrawal, or avoidance of corticosteroids and CNIs. Currently, replacement of a CNI with a mammalian target of rapamycin inhibitor while continuing mycophenolate and discontinuation of corticosteroids within the first post-transplant week is being increasingly utilized. Belatacept-based, CNI-free immunosuppression is an emerging alternative approach to avoiding CNI-mediated nephrotoxicity. We also discuss the evolution, results, and pros and cons of corticosteroid- and CNI minimization protocols. Recent studies suggest that chronic alloimmune damage rather than chronic CNI nephrotoxicity is the major contributor to late kidney allograft failure. The implications of this finding for the use of CNI minimization protocols are also discussed.

Incidence of contrast-induced nephropathy in kidney transplant recipients.

UNLABELLED: Contrast-induced nephropathy (CIN) is responsible for one-third of acute kidney injuries (AKI) in the hospital setting. The incidence of CIN varies from 3% to 30%, depending on the preexisting risk factors, with higher incidence noted with diabetes mellitus, chronic kidney disease, and older age. Though CIN risk factors are common in kidney transplant recipients (KTRs), data about incidence of CIN in this population are sparse. METHODS: We retrospectively analyzed 124 consecutive patients transplanted at our center between January 2002 and December 2013 and received iodinated intravascular contrast with stable kidney function prior to contrast administration. CIN was defined as either an absolute rise in serum creatinine of ≥ 0.5 mg/dL or a ≥ 25% drop in estimated glomerular filtration rate (eGFR) after contrast administration. RESULTS: Seven of 124 (5.64%) patients developed CIN. Kidney function returned to baseline in 5 of the 7 patients within 3 weeks. In 2 patients serum creatinine remained elevated due to recurrent AKI episodes from other causes. Dialysis was not required in any patient. Calcineurin inhibitors (CNIs) were being used in 95% patients at the time of contrast administration. Diabetes mellitus, baseline serum creatinine, age, race, gender, and the use of ACE inhibitor, angiotensin receptor blocker, diuretic, or prophylaxis with intravenous hydration ± N-acetylcysteine did not affect the incidence of CIN. CONCLUSION: Incidence of CIN in KTRs was low in our study (5.6%), much less than previously reported. This low incidence may be related to the high baseline eGFR (>70 mL/min/1.73 m(2)) and use of hypo-osmolar contrast in our patients. In KTRs with baseline eGFR >70 mL/min, the incidence of CIN is low despite the concurrent use of nephrotoxic CNI.

The Utility of Serial Allograft Biopsies during Delayed Graft Function in Renal Transplantation under Current Immunosuppressive Regimens.

Delayed graft function (DGF) of kidney transplants increases risk of rejection. We aimed to assess the utility of weekly biopsies during DGF in the setting of currently used immunosuppression and identify variables associated with rejection during DGF. We reviewed all kidney transplants at our institution between January 2008 and December 2011. All patients received rabbit antithymocyte globulin/Thymoglobulin (ATG) or Basiliximab/Simulect induction with maintenance tacrolimus + mycophenolate + corticosteroid therapy. Patients undergoing at least one weekly biopsy during DGF comprised the study group. Eighty-three/420 (19.8%) recipients during this period experienced DGF lasting ≥1 week and underwent weekly biopsies until DGF resolved. Biopsy revealed significant rejection only in 4/83 patients (4.8%) (one Banff 1-A and two Banff 2-A cellular rejections, and one acute humoral rejection). Six other/83 patients (7.2%) had Banff-borderline rejection of uncertain clinical significance. Four variables (ATG versus Basiliximab induction, patient age, panel reactive anti-HLA antibody level at transplantation, and living versus deceased donor transplants) were statistically significantly different between patients with and without rejection, though the clinical significance of these differences is questionable given the low incidence of rejection. Conclusions. Under current immunosuppression regimens, rejection during DGF is uncommon and the utility of serial biopsies during DGF is limited.

The evolving approach to ethical issues in living donor kidney transplantation: a review based on illustrative case vignettes.

Living donor kidney transplantation which involves performing a major surgical procedure on a healthy person solely to benefit another person has always involved dealing with difficult ethical issues. Beneficence, non-maleficence, donor autonomy, altruistic donor motivation, coercion-free donation, fully informed consent and avoidance of medical paternalism have been the dominant ethical principles governing this field ever since the first successful living donor kidney transplant in 1954. The increasing reliance on living donors due to the rapidly growing disparity between the number of patients awaiting transplantation and the availability of deceased donor kidneys has brought with it a variety of new ethical issues of even greater complexity. Issues such as confidentiality of donor and recipient medical information, the appropriateness of the invented medical excuse to avoid donation and the approach to misattributed paternity discovered during work-up for living donor transplantation have made the information to be disclosed prior to obtaining donor's consent much more extensive. In this article, we review the current thinking and guidelines (which have evolved considerably over the past several decades) regarding these ethical issues using five illustrative case vignettes based on donors personally evaluated by us over the past 35 years.

Renal allograft outcome in recipients of positive-crossmatch combined liver-kidney transplantation.

BACKGROUND: Successful kidney transplantation despite positive crossmatch (+CXM) before transplantation is well recognized in combined liver-kidney transplant (CLKT) recipients. This is probably due to immunologic protection of the renal allograft (RA) conferred by the liver allograft. However, occurrences of antibody-mediated rejection and poor long-term RA outcome is also documented with +CXM CLKT recipients, suggesting that such immunologic protection may not be universal. METHODS: A total of 1,401 CLKT recipients with known status of pre-transplantation CXM were identified from the United Network for Organ Sharing registry from January 1, 1986, to December 31, 2006. Univariate analysis for significant differences in clinical variables and Kaplan-Meier estimate for patient and graft survivals were performed. The results were compared between positive and negative CXM groups. RESULTS: Pre-transplantation +CXM was seen in 17.3% (242/1401) of CLKT recipients studied. The demographic and clinical characteristics were similar between the groups, except for higher panel reactive antibody level and CXM positivity in female recipients. Outcome analysis showed higher RA rejection (19.3% vs 10.8%; P = .026) and increased hospital length of stay (37.3 ± 46.0 vs 28.8 ± 33.2 days; P = .028) in the +CXM group. RA survivals at 1, 3, and 5 years were 8%, 7%, and 6% lower in the +CXM group. The patient and liver allograft survivals were not different between the groups. CONCLUSIONS: In CLKT recipients with pre-transplantation +CXM, the immunologic protection of RA conferred by the liver allograft is less robust than previously perceived and may lead to higher rejection rate and poor RA outcome. This can be mitigated with routine pre-transplantation CXM.

Increasing trend in infection-related death-censored graft failure in renal transplantation.

BACKGROUND: Advances in kidney transplantation have significantly improved early outcomes but failed to improve long-term graft survival. Despite many causes, the contribution of infection to death-censored graft failure (DCGF) is unknown. The aim of our study is to assess the impact of infections on DCGF using United Network for Organ Sharing data. METHODS: We analyzed 38,286 DCGFs among 189,110 first kidney transplants performed between January 1, 1990 and December 31, 2006. Information on infection contributing to DCGF was available in 31,326 DCGF recipients. Student's two-sample t test for normally distributed variables, Wilcoxon rank sum test for nonnormally distributed, and Chi-square test for categorical variables were used in univariable comparisons. Multivariable logistic regression analysis was performed to assess the independent contribution of variables to infection-related DCGF. RESULTS: Overall, infection accounted for 7.7% (2397/31,326) of all DCGF. The rate of infection-related DCGF increased from 6.4% in 1990 to 10.1% in 2006 and was significantly higher during 1997 to 2006 when compared with 1990 to 1996 period (9.1% vs. 6.3%, P<0.001). Over these 17 years, the trends in infection-related DCGF and rejection rates showed an inverse relationship with the former exceeding the latter starting in 2005. The risk of infection-related DCGF was higher (14.1%) in recipients older than 65 years and exceeded the rejection rate in those older than 60 years. Urological complications and polyoma infection were the most significant risk factors with odds ratios of 8.77 (confidence interval: 5.15-14.93) and 2.55 (confidence interval: 1.41-4.61), respectively. CONCLUSION: Infection is increasingly contributing to DCGF in recent years and warrant reevaluation of current immunosuppression protocols, especially in older recipients.

Hepatorenal syndrome.

Acute kidney injury (AKI) secondary to hepatorenal syndrome (HRS) is an ominous complication of end-stage liver disease (ESLD). In HRS, splanchnic and peripheral vasodilatation with reduction in effective arterial volume causes activation of mechanisms leading to intense renal vasoconstriction and functional AKI. HRS is a diagnosis of exclusion and all other causes of AKI (especially prerenal azotemia) have to be considered and excluded. Spontaneous bacterial peritonitis (SBP) frequently precipitates HRS and should be ruled out in all ESLD patients presenting with AKI. Prompt therapy of SBP with intravenous antibiotics and albumin lessens the risk of developing HRS. Combined use of intravenous albumin, splanchnic and/or peripheral vasoconstrictors, and renal replacement therapy (RRT) are only bridges to early liver transplantation (or combined liver-kidney transplantation in selected patients). Transplantation is the only definitive way of improving the long-term prognosis. Close collaboration between hospitalists/internists managing HRS patients and hepatology and nephrology consultants is critically important.

Updated principles and clinical caveats in the management of infection in renal transplant recipients.

Renal transplantation is now considered the treatment of choice for patients with end-stage renal disease. In transplant recipients, infection and rejection are entwined and are unavoidable tribulations unless clinical tolerance becomes a reality. Although rejection rates have significantly decreased with the introduction of newer immunosuppressive agents, infections remain a major cause of morbidity and mortality, and the magnitude of the problem is on the rise. Newer infections are emerging and patterns of known infections are changing. The continuous evolution of donor and recipient characteristics also alters the landscape of infections. In clinical practice, establishing a definite diagnosis of infection in a timely manner remains a challenge in transplant recipients as compared to immunocompetent individuals. Hence a comprehensive knowledge of the principles of management of infections in renal transplant recipients is very essential. In this review, we would like to provide an overview of some of the key principles that we believe are essential in the management of infectious complications in renal transplant recipients with no focus on any individual infection.

Sequestration of active Cryptococcus neoformans infection in the parathyroid gland despite prolonged therapy in a renal transplant recipient.

Disseminated cryptococcal infection occurs mainly in the immunocompromised host, particularly in those with impaired cellular immunity. The treatment outcome depends not only on the duration and choice of antifungal therapy, but also on the activity of the organism to persist in different parts of the body despite therapy. We present a case of persistence of cryptococcal infection in the parathyroid gland in a kidney transplant recipient. A 38-year-old male renal transplant recipient diagnosed to have disseminated cryptococcosis was treated with discontinuation of immunosuppression, amphotericin B, and flucytosine for 2 weeks, and fluconazole subsequently. Dialysis was initiated when graft function deteriorated after discontinuation of immunosuppression. The patient showed no clinical signs of active cryptococcal infection on fluconazole therapy. One year after the diagnosis of cryptococcosis, and still on fluconazole, he underwent parathyroidectomy, for severe secondary hyperparathyroidism. Surprisingly, active cryptococcal infection with necrotizing granulomatous inflammation was demonstrated in the parathyroid, despite being on therapy. This patient illustrates that persistence of fungal infection despite prolonged therapy can occur in unusual sites such as the parathyroid and may be a source for future recurrence and dissemination.

Utility of estimated glomerular filtration rate in live kidney donation.

Live kidney donation is considered safe; nevertheless, data supporting such claims are almost exclusively of white origin with very limited long-term outcomes in ethnic minority donors. This prospective observational study consisted of a total of 103 previous kidney donors (54 black and 49 white) with mean follow-up days of 743.5 +/- 603.9 for white and 845.1 +/- 668.5 for black donors. The black donors had a statistically significant greater loss of estimated GFR (eGFR; 39.8 ml/min per 1.73 m2) in comparison with white donors (30.4 ml/min per 1.73 m2; P = 0.001). In multivariate analysis, predonation eGFR of <100 ml/min and age at the time of donation were the significant predictors for postdonation eGFR <60 ml/min among black donors. Because eGFR using the Modification of Diet in Renal Disease 4 formula is not validated in live kidney donors, the significance of eGFR <60 ml/min per 1.73 m2 in previous kidney donors is unclear. Long-term prospective study with a gold standard method such as iothalamate GFR measurement is needed to define the actual decrease in eGFR after kidney donation.

Quality of life and psychosocial factors in renal transplant recipients.

An ideal method for quality of life (QOL) assessment in renal transplant recipients (RTR) has not yet been determined. Present assessments of QOL in RTR are lengthy, cumbersome to administer, and difficult to interpret. We used a previously validated single question QOL scale score (QLS) that directly asks about the patients' overall assessment of their QOL; "Considering all parts of my life-physical, emotional, social, spiritual, and financial--over the past 2 days the quality of my life has been ... ". The QLS ranges from 0 ("very bad") to 10 ("excellent"). Patients were contacted prior to their routine office visit when they were free of acute medical problems. Fifty RTR participated. Psychosocial and medical variables included the Beck Depression Inventory, Illness Effects Questionnaire, Multidimensional Scale of Perceived Social Support, time since transplant, age, creatinine, hemoglobin, and albumin levels. Of the patients, 64% were African-American and 48% were women; 94% of patients had a score>5. Mean QLS was 7.5+/-2.3. Perception of a better QOL correlated with less perception of depression and illness effects and with perception of greater social support and satisfaction with life (all P<.05). Perception of QOL did not correlate with age, time since transplantation, creatinine, hemoglobin or albumin levels. We concluded that QLS is a quick tool to measure subjective QOL in RTR for correlation with psychosocial factors of interest in this group. These studies should be replicated in larger multiethnic populations.

Comparison of long-term actual renal allograft survival in mycophenolate mofetil and azathioprine-based triple drug immunosuppression protocols.

INTRODUCTION: The use of mycophenolate mofetil (MMF) in renal transplantation results in a 50% lower incidence of acute rejection compared to azathioprine (AZA). However, the graft survival reports are conflicting: the European trial and US database analysis suggest better survival with MMF, an observation that was not seen in the US and tricontinental studies. METHODS: We retrospectively reviewed our single-center experience (60% African-Americans) comparing the serum creatinine (SCr) values and 3-year actual graft survival with MMF versus AZA-based immunosuppression. Group I included patients transplanted between January 1990 and December 1992 on cyclosporine (CSA), AZA, and steroids; group II subjects, from January 1996 to December 1998 on CSA, MMF, and steroids. We analyzed SCr and all causes of graft losses at 3, 6, 12, 18, 24, and 36 months posttransplantation. RESULTS: The patient demographics were similar in both groups as was the mean SCr values at different times. The time-group interaction for SCr, the Kruskal-Wallis test for SCr for different categories (<1.5, 1.5 to 2.0, 2.0 to 2.5, and >2.5 mg/dL) and the all-cause graft loss between the two groups were not significantly different. CONCLUSION: Our results failed to show better long-term actual graft survival despite the 6-year interval between the two groups. These findings agree with the results of the United States and the tricontinental studies. A lower incidence of acute rejection early after transplantation observed with MMF may not always translate into a long-term benefit, possibly due to the influence of nonimmunological factors, such as hypertension, calcineurin inhibitor toxicity, more frequent cytomegalovirus infections, and increased attempts to withdraw steroids using MMF-based protocols.

Rapid resolution of proteinuria of native kidney origin following live donor renal transplantation.

To assess the contribution of the protein content of urine from the native kidneys to post-transplant proteinuria, we prospectively studied 14 live donor transplant recipients with a pre-transplant random urine protein to creatinine ratio (UPr:Cr) >0.5. Seven patients received preemptive transplants, and seven patients were on dialysis pre-transplant (with residual urine output). Resolution of proteinuria was defined as UPr:Cr < 0.2. Immunosuppression consisted of tacrolimus, mycophenolate mofetil and corticosteroids. Anti-hypertensive drugs that might reduce proteinuria were avoided during the study. The serum creatinine was 8.7 +/- 0.7 mg/dL pre-transplant, and the nadir post-transplant serum creatinine was 1.4 +/- 0.1 mg/dL. The pre-transplant UPr:Cr ranged between 0.5 and 9.2 (mean = 2.9 +/- 0.6). The UPr:Cr decreased to <0.2 in all 14 patients at a mean of 4.5 weeks post-transplant (range 1-10 weeks). In conclusion, in live donor renal transplant recipients with immediate graft function, proteinuria of native kidney origin resolves in the early post-transplant period. After the immediate post-transplant period, proteinuria cannot be attributed to the native kidneys, and work up for proteinuria should focus on the allograft.

Outcome of low-dose ganciclovir for cytomegalovirus disease prophylaxis in renal-transplant recipients.

To assess the outcome of low-dose-ganciclovir prophylaxis (500 mg twice a day for 3 months) in renal-transplant recipients, a retrospective analysis of 185 patients transplanted between 1998 and 2001 was performed. There were 29 (15.6%) patients who belonged to the highest risk group, donor cytomegalovirus (CMV) positive, recipient negative (D + R-), and 37 (20%) patients in the lowest risk group, D-R-. Induction immunosuppression consisted of polyclonal antibody or OKT3 (n = 62, 33.5%), interleukin-2 receptor antibody (n = 61, 33%), and no induction (n = 62, 33.5%). CMV disease occurred in 13 (7%) patients. Highest incidence was in D + R- group (17.2%), with no cases in D-R- group (P = 0.03). Tissue-invasive CMV occurred in 4 of these 13 patients. In patients developing CMV disease, there was no evidence of ganciclovir resistance and no mortality over a mean follow-up of 42 months. Low-dose ganciclovir was found to be as effective in decreasing the incidence of clinical CMV disease as high-dose ganciclovir (1 gm three times a day for 3-6 months) in previous studies.

Proteinuria and microalbuminuria in adults: significance, evaluation, and treatment.

This paper reviews current concepts regarding the pathophysiology, diagnostic evaluation, and treatment of microalbuminuria and proteinuria in adults. Microalbuminuria (in diabetics) and proteinuria are early markers for potentially serious renal disease, and are associated with increased risk of atherosclerotic cardiovascular disease. Proteinuria also contributes to renal scarring, and accelerates the progression of chronic kidney disease to end-stage renal failure. Screening of diabetics for microalbuminuria, and the initial workup of proteinuria, should occur in the primary care setting. Reduction of microalbuminuria in diabetics may retard its progression to overt diabetic nephropathy. Therapy of renal diseases should aim for optimal blood pressure control and the maximum possible reduction in urinary protein excretion. Angiotensin-converting enzyme inhibitor (ACE-I) and/or angiotensin-receptor blocker (ARB) therapy is the most effective measure to achieve this. These drugs also provide protection against the cardiovascular problems that are highly prevalent in this patient population.

Rapid progression of native renal artery fibromuscular dysplasia following kidney donation.

Fibromuscular dysplasia is the second commonest anatomical abnormality apart from multiple renal arteries in the potential live donors. Pretransplant evaluation of the donors may include an angiography to evaluate the renal arteries, and failure to recognize renal arterial stenosis, particularly fibromuscular dysplasia, by noninvasive methods may eventually lead to hypertension and ischemic renal failure. We report a case of fibromuscular dysplasia that was undetected by computed tomographic angiography prior to donation. One year after kidney donation, it rapidly progressed to severe symptomatic stenosis with hypertension and acute renal failure. Following renal artery angioplasty, her blood pressure normalized over a period of 2 weeks without any need for antihypertensive medications and the serum creatinine returned to her baseline. The acceptability of renal donors with fibromuscular dysplasia depends on the age, race and the availability of the other suitable donors. Mild fibromuscular dysplasia in a normotensive potential renal donor cannot be considered a benign condition. Such donors need regular follow-up postdonation for timely detection and treatment.