Acute Kidney Failure in a Young African American Male.

Retroperitoneal fibrosis (RPF) is a condition characterized by chronic inflammatory and fibrotic changes in the retroperitoneum that can lead to serious complications including kidney failure, mesenteric and limb ischemia, and deep venous thrombosis among others. Affected individuals may present with nonspecific symptomology that would require a high clinical index of suspicion for prompt diagnosis. We herein discuss a case of a young African-American man with recurrent deep venous thrombosis who presents with a 4-week history of constant aching pain of abdomen and back and kidney failure. Initial noncontrast computed tomogram (CT) only revealed mild bilateral hydroureteronephrosis with inflammatory changes but without obvious mass or lymphadenopathy. At the insistence of the renal consulting team to rule out RPF, a CT-urogram was performed which revealed an infiltrative mass encasing the aorta, inferior vena cava, and common iliac vessels. Laparoscopic biopsy revealed dense fibroadipose tissue, lymphocytic aggregates, focal scattered IgG4-positive plasma cells, and fibrin deposition. Patient underwent bilateral nephrostomy placement and empirical corticosteroid therapy with resolution of kidney failure. Our case illustrates a classic presentation of RPF with relatively benign findings on noncontrast CT that could have been missed if clinicians did not keep a high index of suspicion for the condition.

Cisplatin-Induced Renal Salt Wasting Requiring over 12 Liters of 3% Saline Replacement.

Cisplatin is known to induce Fanconi syndrome and renal salt wasting (RSW). RSW typically only requires transient normal saline (NS) support. We report a severe RSW case that required 12 liters of 3% saline. A 57-year-old woman with limited stage small cell cancer was admitted for cisplatin (80 mg/m2) and etoposide (100 mg/m2) therapy. Patient's serum sodium (SNa) decreased from 138 to 133 and 125 mEq/L within 24 and 48 hours of cisplatin therapy, respectively. A diagnosis of syndrome of inappropriate antidiuretic hormone secretion (SIADH) was initially made. Despite free water restriction, patient's SNa continued to decrease in association with acute onset of headaches, nausea, and dizziness. Three percent saline (3%S) infusion with rates up to 1400 mL/day was required to correct and maintain SNa at 135 mEq/L. Studies to evaluate Fanconi syndrome revealed hypophosphatemia and glucosuria in the absence of serum hyperglycemia. The natriuresis slowed down by 2.5 weeks, but 3%S support was continued for a total volume of 12 liters over 3.5 weeks. Attempts of questionable benefits to slow down glomerular filtration included the administration of ibuprofen and benazepril. To our knowledge, this is the most severe case of RSW ever reported with cisplatin.

Simultaneous liver-kidney transplantation or liver transplantation alone for patients in need of liver transplantation with renal dysfunction.

PURPOSE OF REVIEW: There have been no well defined guidelines to determine whether a kidney transplant should be offered to liver transplant candidates who have chronic kidney disease (CKD) or prolonged acute kidney injury while awaiting a liver transplant. This article provides a review of current literature on risk factors for CKD progression after liver transplantation alone (LTA) in patients with pretransplant renal dysfunction and the utility of cystatin C (Cyst C) to assess renal function in cirrhotic patients. Studies evaluating risk factors for transplant futility are also discussed. Based on available literature and existing consensus guidelines, a proposed algorithm for simultaneous liver-kidney transplantation (SLKT) or LTA is formulated. RECENT FINDINGS: In LTA recipients with pretransplant renal dysfunction, diabetes mellitus and type 2 hepatorenal syndrome are associated with CKD progression posttransplant. Coexisting diabetes and stages 3-4 CKD increase end-stage renal disease risk. Cyst C may be a better marker of renal function in cirrhotics. In LTA recipients, very high MELD scores and the concomitant presence of multiple comorbidities increase liver transplant futility risk. Similar studies in SLKT recipients are lacking. SUMMARY: Pretransplant diabetes status should be incorporated into future guidelines for SLKT, whereas simultaneous kidney transplantation should be deferred in highest acuity SLKT candidates with high kidney transplant futility risk. Cyst C-based equations may allow clinicians to better select the most appropriate candidates for SLKT or LTA. Further studies are needed.

Management of patients with a failed kidney transplant: Dialysis reinitiation, immunosuppression weaning, and transplantectomy.

The number of patients reinitiating dialysis after a failed transplant increases over time and has more than doubled between the year 1988 and 2010 (an increase from 2463 to 5588). More importantly, patients returning to dialysis have been shown to have a greater than three-fold increase in the annual adjusted mortality rates compared with those with a functioning graft. Continuation of immunosuppression to preserve residual graft function has been implicated to be a contributing factor, seemingly due to immunosuppression-associated cardiovascular and infectious complications and malignancy risk, among others. Nonetheless, maintenance low-dose immunosuppression has been suggested to confer survival benefit in patients returning to peritoneal dialysis. Whether early vs late reinitiation of dialysis or whether transplantectomy has an impact on patient survival remains poorly defined. Consensus guidelines for the management of a failed allograft are lacking. In this article, we present a literature overview on the ideal timing of dialysis reinitiation after graft loss, the management of immunosuppression after graft failure, and the risks and benefits of transplantectomy. The authors' perspectives on the management of this special patient population are also discussed.

Kidney retransplantation for BK virus nephropathy with active viremia without allograft nephrectomy.

BK virus nephropathy is an important cause of kidney allograft failure. Retransplantation has been successfully performed for patients with previous allograft loss due to BK virus nephropathy; however, whether allograft nephrectomy and viral clearance are required prior to retransplantation is controversial. Some recent studies have suggested that retransplantion can be successfully achieved without allograft nephrectomy if viremia is cleared prior to retransplant. The only published experience of successful retransplantation in the presence of active viremia occurred in the presence of concomitant allograft nephrectomy of the failing kidney. In this report, we describe a case of successful repeat kidney transplant in a patient with high-grade BK viremia and fulminant hepatic failure without concomitant allograft nephrectomy performed under the setting of a simultaneous liver-kidney transplant.

BK virus infection following kidney transplantation: an overview of risk factors, screening strategies, and therapeutic interventions.

PURPOSE OF REVIEW: In recipients of kidney transplants, the emergence of BK virus (BKV)-associated clinical syndromes, such as viruria, viremia, and BK nephropathy, coincided with the advent of potent immunosuppressive therapy. There is currently no standardized protocol for the management of BK viruria or viremia, or established BK nephropathy. Suggested risk factors for BKV replication and a literature overview on various treatment strategies for BKV-associated clinical syndromes are presented, followed by the authors' proposed approach for screening, monitoring, and treatment of post-transplant BKV infection. RECENT FINDINGS: BKV infection can occur under all combinations of immunosuppressive therapy. Although both humoral and cellular immunity may be essential, BKV-specific T-cell immunity appears to play a pivotal role in controlling BKV replication. Monitoring BKV-specific immune response might prove useful in guiding therapeutic intervention. The beneficial effects of antiviral agents remain unclear. Development of T-cell or antibody-based vaccines against BKV is a subject of future research. SUMMARY: In the absence of conclusive evidence that any particular immunosuppressive agent has a specific influence over another on BKV infection risk and the unclear benefit of antiviral agents, intensive monitoring of serum BKV using PCR and immunological containment of BKV replication should remain the mainstay of therapy. The routine recommendations of antiviral agents in the treatment of BKV-associated clinical syndromes await results of large prospective randomized trials.

Immunosuppressive management of dialysis patients with recently failed transplants.

Over the past decade, patients returning to dialysis after a failed transplant comprised of 5-10% of the annual number of dialysis initiations in the United States, whereas retransplant candidates account for 5.0-13% of the annual deceased donor wait-list additions. The United States Renal Data System (USRDS) database revealed a >3-fold increase in the annual adjusted death rates for patients returning to dialysis after graft loss compared with patients with a functioning allograft (9.4% vs. 2.8%, respectively). Continuation of low-dose immunosuppression to maintain residual allograft function has been suggested as a contributing factor, presumably via treatment-related infectious and cardiovascular complications among others. In contrast, a survival advantage in maintaining patients on long-term immunosuppression after returning to peritoneal dialysis has also been suggested. Despite the significant number of patients requiring reinitiation of some form of renal replacement therapy after a failed transplant and the increasing evidence suggesting their high mortality and morbidity rates, management of the failed allograft in these patients has received little attention. This article presents an overview of the literature on the management of immunosuppression after allograft failure, a brief review on the pros and cons of allograft nephrectomy, and the authors' opinions on the management of immunosuppression in patients with a failed kidney allograft.

ABO blood type-incompatible kidney transplantation and access to organs.

OBJECTIVE: To determine whether ABO-incompatible (ABOi) kidney transplantation can be performed safely and result in acceptable posttransplantation outcomes. DESIGN: Prospective study. SETTING: Transplantation center. PATIENTS: In the 1½ years of a new program, 18 patients with renal failure and an ABOi living kidney donor were included in the study. All donors and recipients were of incompatible blood types and underwent transplantation beginning in June 2008. INTERVENTIONS: Patients received immunomodulation (anti-CD20 antibody, intravenous immunoglobulin, and plasmapheresis) until an acceptable isoagglutinin titer was obtained on the date of transplantation. All the kidneys were transplanted heterotopically, and all the patients received induction immunosuppression followed by a combination of prednisone, mycophenolate mofetil, and tacrolimus. Isoagglutinin titers were monitored, and postoperative plasmapheresis was initiated if titers increased. MAIN OUTCOME MEASURES: Patient and allograft survival; length of stay; 1-, 3-, and 6-month and 1-year renal function; and incidence of rejection. RESULTS: Patient survival was 100%, with allograft survival of 94.4%. Mean (SD) length of stay was 6.9 (1.9) days. Donor to recipient transplantation was A to O in 11 cases, A2 to B in 1, B to A in 3, B to O in 1, and AB to B in 2. Mean (SD) creatinine levels, a measure of graft function, were 1.2 (0.5) mg/dL at discharge, 1.4 (0.4) mg/dL at 1 month, 1.3 (0.45) mg/dL at 3 months, 1.1 (0.3) mg/dL at 6 months, and 1.2 (0.2) mg/dL at 1 year. One episode of cellular rejection occurred. CONCLUSIONS: These short-term results suggest that with a straightforward regimen, ABOi kidney transplantation is possible, acceptable results and graft function are obtainable, and access to kidney transplantation for those with a blood type-incompatible donor can be expanded.

Evaluation of adult kidney transplant candidates.

Important advances in immunosuppressive therapy and refinement in surgical techniques have allowed renal transplantation to become the treatment of choice for virtually all suitable candidates with end-stage renal disease. Compared to dialysis, kidney transplantation improves both patient survival and quality of life and, over time, can reduce the total cost of medical care. It must be noted, however, that although the risk of death in the first year after transplantation is <5%, not all patients qualify for the surgery because of their unacceptable risks for complications. The transplant evaluation process requires a comprehensive assessment of each patient's medical, surgical, and psychosocial histories. Selection of the suitable transplant candidate remains a challenge for transplant physicians owing, predominantly, to the presence of complex medical issues in the potential candidates and nonstandardized criteria for acceptance or rejection among transplant centers. Furthermore, with the ever-increasing disparity between donor organ supply and demand and resultant increased wait-list times, the transplant physicians must further consider the optimal management and re-evaluation of wait-list patients during the waiting period. This article describes a systematic approach for the evaluation of a potential renal transplant candidate. Various medical issues that arise during the evaluation process are discussed.

Thrombotic microangiopathy following pancreas after kidney transplants.

Advances in immunosuppressive therapy and refinement in surgical techniques have allowed pancreas after kidney (PAK) transplantation to become a viable therapeutic option for patients with brittle type I diabetic recipients of a living donor or previous deceased kidney alone transplant. Although maintenance immunosuppressive therapy is not significantly changed after the addition of a pancreas, a temporary booster in immunosuppressive therapy and an increase in the dose of calcineurin inhibitor (CNI) are required after PAK transplantation. The latter has been implicated in the observed variable decline in kidney allograft function. We herein report two cases of kidney allograft dysfunction following PAK transplant due to biopsy-proven transplant, thrombotic microangiopathy (TMA). Whether PAK transplantation pre-disposes a subset of patients to the development of post-transplant TMA is not known. Diagnostic kidney biopsies should be considered in PAK transplant recipients with worsening kidney allograft function.

Outcomes of dual adult kidney transplants in the United States: an analysis of the OPTN/UNOS database.

BACKGROUND: The organ shortage has resulted in increased use of kidneys from expanded criteria donors (ECD). For ECD kidneys unsuitable for single use, dual kidney transplants (DKT) may be possible. There are limited data comparing outcomes of DKT to single kidney ECD transplants, making it unclear where DKT fits in the current allocation scheme. Our purpose was to compare outcomes of DKT and ECD transplants in the United States. METHODS: From 2000 to 2005, a total of 625 DKT, 7686 single kidney ECD, and 6,044 SCD transplants from donors aged>or=50 years were identified from the Organ Procurement and Transplantation Network/United Network for Organ Sharing data. Allograft survival was the primary outcome. RESULTS: DKT comprised 4% of kidney transplants from donors aged>or=50 years. Compared to the ECD donor group, the DKT donor group was older (mean age 64.6+/-7.7 years vs. 59.9+/-6.2 years) and consisted of more African Americans (13.1% vs. 9.9%), and more diabetic donors (16.3% vs. 10.4%; P<0.001). Mean cold ischemic time was longer in DKT (22.2+/-9.7 hr), but rates of delayed graft function were lower (29.3%) compared to ECD transplants (33.6%, P=0.03). Three-year overall graft survival was 79.8% for DKT and 78.3% for ECD transplants. CONCLUSION: DKT were infrequent and had outcomes comparable to ECD transplants, despite the use of organs from higher risk donors. With a more upfront approach to DKT by offering this option to patients at the time of wait-listing as part of an ECD algorithm, we may be able to further optimize outcomes of DKT and minimize discard of potential organs.

Donor biopsy and kidney transplant outcomes: an analysis using the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) database.

BACKGROUND: Although the degree of glomerulosclerosis on pretransplant donor biopsy is one criterion used in the decision to accept a deceased donor kidney, its relationship with graft survival remains controversial. This study compared graft survival with the degree of glomerulosclerosis found on donor biopsy. We also examined the agreement in degree of glomerulosclerosis between paired kidneys. METHODS: Biopsy results from 12,129 adult deceased donor transplants between January 1, 2000 and December 31, 2005 were identified in the Organ Procurement and Transplantation Network/United Network for Organ Sharing data, as of September 11, 2006. Of these, 2696 donors had both kidneys biopsied and subsequently transplanted. RESULTS: Among the groups with greater than 5% glomerulosclerosis, there was no statistically significant difference in graft survival rates (log-rank, P=0.44). The overall graft survival rates of the 0-5% group were significantly superior to those of the >5% groups (1-, 3-, and 5-year rates: 85.9%, 72.4%, and 59.0% for 0-5% group vs. 81.6%, 68.1%, and 53.6% for >5% group, log-rank P<0.001). Agreement between paired kidneys from the same donor was highest for the 0-5% glomerulosclerosis groups (90.6% for pairs with 0-5% glomerulosclerosis in the left kidney vs. 42.5% for pairs with >5% glomerulosclerosis in the left kidney). CONCLUSION: Donor kidneys with less than 6% glomerulosclerosis were associated with better graft outcomes and intrapair agreement in the degree of glomerulosclerosis. Among kidneys with greater than 5% glomerulosclerosis, the degree of glomerulosclerosis did not help predict graft outcomes. Sampling error may contribute to the lack of outcome differences seen among these kidneys, given the low intrapair agreement.

Concurrent FSGS and Hodgkin's lymphoma: case report and literature review on the link between nephrotic glomerulopathies and hematological malignancies.

BACKGROUND: The link between the nephrotic syndrome (NS) and malignancy was first described in 1922. In solid tumors, the NS is most often due to membranous glomerulonephropathy, whereas in common hematological malignancies, minimal-change disease predominates. Focal segmental glomerulosclerosis (FSGS) is among the least frequently reported renal lesion associated with malignancy. METHODS: We report a case of the simultaneous diagnoses of FSGS and Hodgkin's lymphoma, and review the literature on various nephrotic glomerulonephropathies associated with common leukemia and lymphoma. RESULTS: Although nephrotic glomerulonephropathies rarely occur in association with acute leukemia, they have often been described in chronic lymphocytic leukemia (CLL). Membranoproliferative glomerulonephropathy and membranous glomerulonephropathy are the most common lesions observed in CLL. Nephrotic glomerulonephropathies have also been well documented among patients with lymphomas, in particular, Hodgkin's lymphoma. While minimal-change disease is most commonly found in association with Hodgkin's lymphoma, more diverse and complex renal lesions are associated with non-Hodgkin's lymphoma. FSGS remains a rare association with hematological malignancies. CONCLUSIONS: Nephrotic glomerulonephropathies are not only linked to solid-organ tumors, but also to hematological malignancies. A thorough evaluation, including a physical examination for lymphadenopathy and organomegaly, as well as a hematological evaluation, must be performed in all patients presenting with nephrotic glomerulonephropathies.

Noninvasive diagnosis of cellular and antibody-mediated rejection by perforin and granzyme B in renal allografts.

A major milestone in transplantation would be the use of biomarkers to monitor rejection. We examined the association between perforin and granzyme-B gene expression detected in the peripheral blood of renal allograft recipients with cellular and antibody-mediated rejection. Furthermore, we judged the appropriateness of assigning negative rejection statuses to persons without a biopsy whose grafts were functioning well clinically. Of the 46 patients who completed the study, recipients with cellular rejection had higher perforin and granzyme-B levels compared with nonrejectors (p = 0.006). Interestingly, recipients with antibody-mediated rejection also had higher perforin and granzyme-B levels compared with nonrejectors (p = 0.04). Patients with high levels of granzyme B had a probability of rejecting that was 26.7 times greater than those patients with low levels of granzyme B. Perforin and granzyme B had sensitivities of 50% and specificities of 95% in predicting rejection (cutoff value = 140). Assigning negative rejection statuses to recipients without a biopsy whose grafts were functioning well did not have a major effect on the direction or significance of covariate values. This study suggests that perforin and granzyme-B gene expressions in peripheral blood are accurate in detecting both cellular and antibody-mediated rejection.

Sirolimus-associated pulmonary toxicity.

BACKGROUND: Pulmonary toxicity has recently been recognized as a potentially serious complication associated with sirolimus therapy. We further detail this condition on the basis of our own cases and those reported in the literature. METHODS: We report three cases of suspected sirolimus-induced pulmonary toxicity that occurred in three renal transplant recipients and searched PubMed for all previously reported cases. RESULTS: Including our current cases, 43 patients with sirolimus-induced pulmonary toxicity have now been reported. Clinical data were incomplete in 28 cases. Analysis of available data for 15 patients revealed that the most commonly presenting symptoms were dyspnea on exertion and dry cough followed by fatigue and fever. Chest radiographs and high-resolution computed tomography scans commonly revealed bilateral patchy or diffuse alveolo-interstitial infiltrates. Bronchoalveolar fluid analysis and lung biopsy in selected case reports revealed several distinct histologic features, including lymphocytic alveolitis, lymphocytic interstitial pneumonitis, bronchoalveolar obliterans organizing pneumonia, focal fibrosis, pulmonary alveolar hemorrhage, or a combination thereof. The diagnosis of sirolimus-associated pulmonary toxicity was made after an exhaustive work-up to exclude infectious causes and other pulmonary disease. Sirolimus discontinuation or dose reduction resulted in clinical and radiologic improvement in all 15 patients within 3 weeks. CONCLUSION: The temporal relationship between sirolimus exposure and onset of pulmonary symptoms in the absence of infectious causes and other alternative pulmonary disease and the associated clinical and radiologic improvement after its cessation suggests a causal relationship. Because the use of sirolimus in organ transplantation has become more widespread, clinicians must remain vigilant to its potential pulmonary complication.