Dual kidney transplantation: a single-center experience.

BACKGROUND: Dual kidney transplantation (DKT) is an alternate approach to use marginal kidneys not suitable to be allocated for single kidney transplant. This retrospective study reviewed the short- and long-term outcomes regarding graft and patient survivals over a 9-year period at a single center. METHODS: From 2005 to 2013, 33 DKTs were performed in our unit, where allocation was guided by clinical parameters mainly. The mean ages for recipients and donors were 58.6 ± 12.5 and 54.8 ± 13.6 years, respectively. Cold ischemia time was 21.4 ± 4 hours, and mean HLA mismatch for HLA-A, HLA-B, and HLA-DR was 3.06 ± 1.07. Immunosuppression regime was tacrolimus based. RESULTS: Median follow-up time of 56 months showed patient and death-censored graft survivals at 1, 3, and 5 years to be 90% and 84%, 90% and 81%, and 84% and 81%, respectively. The rate of delayed graft function was 46.9% (n = 15), the rate of primary graft function was 46.9% (n = 15), the rate of and primary graft nonfunction was 6.2% (n = 2). Nineteen patients (59.4%) required biopsy: 12 of them showed acute tubular necrosis and 7 had rejection (1 needed graft removal, 4 were treated successfully with steroid and/or antithymocyte globulin, and 2 did not require treatment). CONCLUSIONS: Outcomes of DKT in our center were satisfactory and similar to those of other transplant centers regarding patient and graft survivals.

Nephroprotective effects of subcapsular transplantation of metanephric mesenchymal cells on gentamicin-induced acute tubular necrosis in rats.

BACKGROUND: The subcapsular transplantation of metanephric mesenchymal cells (MMCs) may be a new therapeutic approach for the treatment of acute tubular necrosis (ATN). To investigate this hypothesis and provide evidence for its possible use in the clinic, we evaluated the nephroprotective effects of transplanting MMCs into the renal subcaspsule of rats with ATN induced by gentamicin. METHODS: MMCs were expanded in culture. After gentamicin-induced ATN was established, fluorescently-labeled cells were transplanted and traced in kidney tissues by fluorescence microscopy. Serum creatinine (Cr), urea nitrogen (BUN), and N-acetyl-b-D-glucosaminidase (NAG) levels were determined at different time points. Kidney pathology was studied by hematoxylin-eosin staining. Apoptosis was examined by the TUNEL assay. RESULTS: In the MMCs-treated group, the mortality rate decreased; BUN, Cr, and NAG levels peaked at 8 days, and were significantly lower than those in the other groups at 11 and 14 days. RIMM-18 cells locally recruited through precise tropism to sites of injury had the ability to migrate into the tubuli from the renal subcapsule. Damage to the cell-treated kidneys was reduced. The pathologic lesion scores of tubular damage reached the highest values at 8 days in the treated kidneys and 11 days in the untreated ones. The apoptotic index showed that the peaks of apoptosis occurred at earlier stages of the injury process in cell-treated than in untreated kidney and thereafter declined in a time-dependent manner. CONCLUSION: The subcapsular transplantation of MMCs could ameliorate renal function and repair kidney injury.

Protective effect of human amniotic fluid stem cells in an immunodeficient mouse model of acute tubular necrosis.

Acute Tubular Necrosis (ATN) causes severe damage to the kidney epithelial tubular cells and is often associated with severe renal dysfunction. Stem-cell based therapies may provide alternative approaches to treating of ATN. We have previously shown that clonal c-kit(pos) stem cells, derived from human amniotic fluid (hAFSC) can be induced to a renal fate in an ex-vivo system. Herein, we show for the first time the successful therapeutic application of hAFSC in a mouse model with glycerol-induced rhabdomyolysis and ATN. When injected into the damaged kidney, luciferase-labeled hAFSC can be tracked using bioluminescence. Moreover, we show that hAFSC provide a protective effect, ameliorating ATN in the acute injury phase as reflected by decreased creatinine and BUN blood levels and by a decrease in the number of damaged tubules and apoptosis therein, as well as by promoting proliferation of tubular epithelial cells. We show significant immunomodulatory effects of hAFSC, over the course of ATN. We therefore speculate that AFSC could represent a novel source of stem cells that may function to modulate the kidney immune milieu in renal failure caused by ATN.

Late spontaneous kidney graft decapsulation after administration of sirolimus in a recipient with chronic hepatitis B and C infection: a case report.

Late spontaneous kidney graft decapsulation with fluid collection is a rare condition with only a few cases reported in the literature. Common causes of renal allograft rupture include acute rejection, acute tubular necrosis, renal vein thrombosis, and trauma. Sirolimus related late spontaneous decapsulation has not been reported in the past. Interestingly, sirolimus may promote lymphocele formation in renal transplant recipients, including those presenting with chronic hepatitis B or C. Herein, we report a case of late spontaneous decapsulation with subcapsular hematoma formation developing 12 years after receipt of a cadaveric allograft. The patient was infected with both hepatitis B and C viruses. Cyclosporine was replaced by sirolimus for maintenance therapy because of chronic rejection and acute deterioration of renal function. He presented to the hospital at 9 months after sirolimus inception because of a sudden onset of pain and swelling over the kidney graft. Magnetic resonance imaging found the capsule to be stripped from the kidney by a collection of liquefied hematomas. A laparoscopic fenestration was performed by creation of a peritoneal window adjacent to the renal allograft. When patients have chronic hepatitis, tacrolimus might be a better choice than sirolimus.

Attenuation of glycerol-induced acute kidney injury by previous partial hepatectomy: role of hepatocyte growth factor/c-met axis in tubular protection.

BACKGROUND/AIMS: Previous partial hepatectomy (HPTX) can attenuate glycerol-induced acute kidney injury (Gly-AKI). The aim of this study was to explore the pathophysiological mechanisms and the role of hepatocyte growth factor (HGF) in kidney protection. METHODS: Rats were subjected to HPTX 24 h before glycerol administration. Renal function, acute tubular necrosis, apoptosis, leukocyte infiltration, and the expression of HGF, c-met, monocyte chemoattractant protein-1, interleukin-1beta, and heme oxygenase-1 were evaluated 24 h after glycerol injection. The regenerative response was analyzed from 6 to 72 h after glycerol injection (BrdU incorporation). In a separate series of experiments, Gly-AKI+HPTX rats were treated with anti-HGF antibody. RESULTS: Gly-AKI+HPTX rats showed an increased expression of renal HGF and c-met as well as an improved creatinine clearance and reduced acute tubular necrosis and apoptosis, cytokine expression, and leukocyte infiltration. The regenerative response was less intense 24 and 72 h after glycerol administration in this group. The anti-HGF treatment disclosed an important role of HGF in the reduction of tubular injury, particularly apoptosis. Overexpression of heme oxygenase-1 was observed in Gly-AKI+HPTX rats, but was not associated with HPTX-induced renal protection. CONCLUSION: We conclude that Gly-AKI+HPTX rats have a reduced susceptibility to renal injury instead of an increased regenerative response and that endogenous HGF overexpression is responsible for suppression of tubular apoptosis.

[Living unrelated renal transplantation in an eldery couple: a case report].

We present a 60-year-old female who underwent living unrelated renal transplantation from her 62-year-old husband. The primary immunosuppression consisted of tacrolimus, mycophenolate mofetil and steroid. We did not recognize any rejection in a histopathological study. The total ischemic time to carry out anastomosis of the two renal arteries was 121 minutes. After hemodialysis 5 times for acute tubular necrosis, her renal function improved. She was discharged on the 33rd postoperative day when her serum cretinine level was 1.0 mg/dl. The graft function was stable at 6 months after transplantation. We discussed living unrelated renal transplantation in the elderly population in Japan.

C4d as a significant predictor for humoral rejection in renal allografts.

OBJECTIVE: To determine the diagnostic and clinical significance of C4d accumulation in renal allografts followed by acute rejection. METHODS: A total of 158 graft biopsies performed from December 1997 to December 2002 were classified, according to the Banff-97 criteria, into hyperacute rejection (HAR, three cases), acute vascular rejection (AVR, 27), acute cellular rejection (ACR, 24), borderline rejection (BR, 38), acute tubular necrosis (ATN, five), stable graft function (SGF, 30) and baseline kidney (31). Immunohistochemical technique was used to determine the C4d deposition level. RESULTS: The percentages of C4d positive in HAR, AVR, ACR, BR, ATN, SGF and baseline kidney groups were 100% (3/3), 77.8% (21/27), 37.5% (9/24), 23.7% (9/38), 0% (0/5), 3.3% (1/30), 0% (0/31), respectively. In acute rejection patients, the peak serum creatinine (sCr) level in C4d(ptc)-positive group (41 cases) was 334.82 +/- 238.37 micromol/L, with that of C4d(ptc)-negative group (47 cases) being 220.20 +/- 176.94 micromol/L (p < 0.01). After treatment, the trough sCr level in C4d(ptc)-positive group and C4d(ptc)-negative group were 176.87 +/- 111.80 and 121.75 +/- 34.59 micromol/L (p < 0.01), respectively. In each AVR, ACR and BR subgroups, the peak sCr level, the trough sCr level, after 3 or 6 months of AR, the sCr level in C4d(ptc)-positive subgroup was higher than that of C4d(ptc)-negative subgroup. There were more resistance against steroid therapy [65.9% (27/41) vs. 36.2% (17/47), p = 0.005] and a higher rate of graft loss [29.3% (12/41) vs. 6.4% (3/47), p = 0.001] in C4d(ptc)-positive group than those of C4d(ptc)-negative group. In each C4d(ptc)-positive subgroup of AVR, ACR and BR the complete reversion was 57.1, 56 and 66.7%, respectively, it is almost same. CONCLUSION: The C4d deposition level is of great value in diagnosis of acute rejection caused by humoral immune components. It is a significant predictor of graft survival and will be of great help when treating acute rejection.

Acute renal failure following multiple wasp stings.

We report the cases of two patients who developed acute renal failure following multiple wasp stings. Both patients required dialysis and recovered within 4 weeks. The kidney biopsy from one patient showed acute tubular necrosis with interstitial nephritis. One patient had complete recovery of renal function on follow-up, while the other was lost to follow-up.

Ten-year experience in the use of double balloon catheter for kidney procurement from non-heart beating donors in cadaveric kidney transplantation.

One-hundred-and-twenty patients underwent first cadaveric kidney transplantation from the non-heart beating donors. All of the organs were procured with the use of double balloon catheter for in situ cooling. The mean warm ischemic time and cold ischemic time were 10.7 +/- 17.0 minutes and 18.9 +/- 11.4 hours, respectively. One- and 5-year graft survival rates were 85.0 and 72.7%, respectively. Among 120 recipients, 30 (25%) grafts functioned immediately (immediate function), 82 (68.3%) grafts functioned after varying length of oliguric periods (delayed function) and 8 (6.7%) grafts never functioned (non-function). The mean age of the donors in the group of immediate function (31.5 +/- 16.1 yr) was significantly lower than those of other two groups. The mean warm ischemic time in the group of immediate function (6.0 +/- 11.2 min) was significantly shorter than that of delayed function. However, there was no significant difference in donor hypotensive episode, types of preservation fluid and cold ischemic time between the groups. The conclusion is that the ultimate result of cadaveric kidney transplant from the non-heart beating donors with the use of double lumen catheter is acceptable despite a relatively high incidence of delayed graft function.

Erythropoietin deficiency in acute tubular necrosis.

Serum erythropoietin (EPO) concentrations were markedly depressed relative to the degree of anaemia in 10 patients with acute tubular necrosis, and remained low long after restoration of excretory renal function as estimated by glomerular filtration rate. Evidence is presented that the low serum EPO level is due to defective synthesis and not to increased catabolism. It is suggested that the predominantly are generatory anaemia found in prolonged cases of acute tubular necrosis, and the slow restoration of red cell mass during recovery, are due to the deficient synthesis of EPO. A positive erythropoietic response in a therapeutic trial with recombinant human erythropoietin (rhEPO) appears to support this hypothesis.

OKT3 prophylaxis in cadaveric kidney transplant recipients with delayed graft function.

Decreased 1-year allograft survival rates have frequently been observed in cadaveric renal allograft recipients with postoperative acute tubular necrosis (ATN), even in the cyclosporine era. Use of cyclosporine despite ATN may lead to a prolongation of ATN, while withholding cyclosporine may increase the chance of an early rejection episode. Prophylactic polyclonal antilymphocyte antibodies have been used postoperatively to prevent rejection while avoiding cyclosporine nephrotoxicity. Since January 1987, the authors have used OKT3 monoclonal antibody prophylaxis in all cadaver kidney recipients with ATN (n = 26). The posttransplant course of these patients was compared with that of cadaveric kidney recipients with ATN who received transplants in 1985-1986 and were treated with cyclosporine during ATN (n = 40). Allograft survival rates in these patients were also compared with those observed in cadaver kidney recipients with immediate graft function. The 1-year graft survival rate was significantly better in the ATN patients who received OKT3 prophylaxis (83%) than in those who were treated early with cyclosporine during the period of ATN (55%). The mean duration of OKT3 therapy was 11.1 +/- 2.5 days. There was no significant difference in 1-year graft survival rates between the ATN patients treated with OKT3 prophylaxis and patients who had immediate graft function (74%, 1985 through 1988 combined). Patient survival was unaffected by the occurrence of ATN or the postoperative immunosuppressive protocol. The duration of ATN was shortened (9.3 +/- 4.0 v 14.9 +/- 10.2 days), and the median time to first rejection was prolonged (23.5 v 11.0 days) by OKT3 prophylaxis compared with early cyclosporine.(ABSTRACT TRUNCATED AT 250 WORDS)

Bilateral total ureteric bypass in the management of renal tubular acidosis.

Nephrocalcinosis and the subsequent obstruction of the ureters by urinary calculi can be a major problem in the management of a patient with renal tubular acidosis. We describe the case history of a girl with this condition in whom the interposition of segments of ileum between the kidneys and bladder, thus bypassing the ureters, had been used in an attempt to overcome the problem of recurrent ureteric obstruction by calculi.