Early Presence of Calcium Oxalate Deposition in Kidney Graft Biopsies is Associated with Poor Long-Term Graft Survival

Accumulated oxalate will be excreted after renal transplantation, creating an increased risk of tubular precipitation, especially in the presence of allograft dysfunction. We evaluated calcium oxalate (CaOx) deposition in renal allograft biopsies with early dysfunction, its association with acute tubular necrosis (ATN) and graft survival. We studied 97 renal transplant patients, submitted to a graft biopsy within 3 months post-transplant, and reanalyzed them after 10 years. We analyzed renal tissue under polarized light and quantified CaOx deposits. CaOx deposits were detected in 52.6% of the patients; 26.8% were of mild and 25.8% of moderate intensity. The deposits were more frequent in biopsies performed within 3 weeks post-transplant (82.4 vs. 63.0%, p < 0.05) and in allografts with more severe renal dysfunction (creatinine 5.6 mg/dL vs. 3.4 mg/dL, p < 0.001). ATN incidence was also higher in patients with CaOx deposits (47% vs. 24%, p < 0.001). Twelve-year graft survival was strikingly worse in patients with CaOx deposits compared to those free of deposits (49.7 vs. 74.1%, p = 0.013). Our study shows a high incidence of CaOx deposits in kidney allografts with early dysfunction, implying an additional risk for acute tubular injury, with a negative impact on graft survival.     

Acute Oxalate Nephropathy Causing Late Renal Transplant Dysfunction Due to Enteric Hyperoxaluria

Calcium oxalate (CaOx) deposition in the renal allograft is an under recognized and important cause of acute tubular injury and early allograft dysfunction.
We present a case of late transplant dysfunction due to acute oxalate nephropathy. The patient presented with diarrhea and deteriorating graft function, and a diagnosis of enteric hyperoxaluria secondary to pancreatic insufficiency was made. This had occurred, as the patient had been noncompliant with his pancreatic enzyme replacement therapy. Treatment to reduce his circulating oxalate load was initiated, including twice-daily hemodialysis, low fat and oxalate diet and appropriate administration of pancreatic enzyme supplements. Graft function subsequently recovered.
The possibility of fat malabsorption leading to enteric hyperoxaluria should be considered in renal graft recipients presenting with loose stools and graft dysfunction.     

Transplanting kidneys from CMV-seropositive donors to CMV-seronegative recipients is not associated with poorer renal allograft function or survival.

BACKGROUND: Cytomegalovirus (CMV)-seronegative recipients of renal allografts from CMV-seropositive donors (D+/R-) have a higher rate of acute rejection than other renal transplant recipients. A relationship between CMV infection/disease and chronic allograft nephropathy (CAN) has been proposed from animal studies, although human studies have been inconclusive. The objective of this study was to determine if CMV seromatching has an effect on renal allograft function and allograft survival. METHODS: A retrospective single centre study was carried out in 333 first cadaveric transplant recipients from January 1, 1991 to December 31, 1997. The primary end-point was creatinine clearance at 3 years post-transplant in groups based on CMV seromatching. The secondary end-point was renal allograft survival. RESULTS: Mean creatinine clearance 3 years post-transplant was 53.4 ml/min/1.73 m2 of body surface area. There was no significant difference in the mean creatinine clearance for groups formed on the basis of CMV seromatching. Delayed graft function and acute rejection were associated with a lower creatinine clearance at 3 years and reduced overall graft survival [hazard ratios 2.35 (1.56-3.54) (P<0.001) and 1.57 (1.0-2.46) (P = 0.046), respectively]. Considering the end-point of graft loss due to acute rejection (censoring for death with a functioning graft) identified the D+/R- group as having an increased hazard of graft loss due to acute rejection [hazard ratio 3.12 (1.16-8.57) (P = 0.024)]. CONCLUSIONS: The D+/R- group does not appear to have poorer renal allograft function 3 years post-transplant. This group does, however, have an increased risk of early allograft loss due to acute rejection.     

Enteric Oxalate Nephropathy in the Renal Allograft: An Underrecognized Complication of Bariatric Surgery

Enteric hyperoxalosis is a recognized complication of bariatric surgery, with consequent oxalate nephropathy leading to chronic kidney disease and occasionally end‐stage renal failure. In patients with prior gastrointestinal bypass surgery, renal allografts are also at risk of oxalate nephropathy. Further, transplant recipients may be exposed to additional causes of hyperoxalosis. We report two cases of renal allograft oxalate nephropathy in patients with remote histories of bariatric surgery. Conservative management led to improvement of graft function in one patient, while the other patient returned to dialysis. Interpretation of serologic, urine and biopsy studies is complicated by oxalate accumulation in chronic renal failure, and heightened excretion in the early posttransplant period. A high index of suspicion and careful clinicopathologic correlation on the part of transplant nephrologists and renal pathologists are required to recognize and treat allograft oxalate nephropathy. As the incidence of obesity and pretransplant bariatric surgery increases in the transplant population, allograft oxalate nephropathy is likely to be an increasing cause of allograft dysfunction.     

Peritubular capillary C4d staining in late acute renal allograft rejection – is it relevant?

Abstract: Background: In the early post-transplant period, renal allograft rejection with diffuse peritubular capillary (PTC) C4d deposition predicts poor graft survival. In the late post-transplant setting, that is, one or more yr after transplantation, the implication of diffuse PTC C4d deposition is still a topic of debate. The purpose of our study was to see if diffuse PTC C4d deposition, in late acute rejection (LAR), occurring more than one yr post-transplant, has any impact on graft survival and function. Methods: We selected cases, both cadaveric as well as living donor renal transplant recipients, in whom acute rejection with PTC C4d deposition was first detected after the first year post-transplant. Recipients with multiple acute rejection episodes during the first year post-transplant were excluded from the study. The first biopsy diagnosed with LAR was considered the index biopsy (n = 40). We formed two groups: group 1, C4d-positive LAR (n = 20), and group 2, C4d-negative LAR (n = 20). Groups were matched for maintenance and post-rejection immunosuppressive therapy, baseline serum creatinine levels before the time of the index biopsy, time from transplant to index biopsy, as well as chronic allograft damage index (CADI) score in the index biopsies. We compared the rate of graft loss, and the graft function of the surviving grafts at the end of the study period, as well as histologic parameters in the index biopsy specimens between the two groups. The mean follow-up period was 20 months. Results: No significant differences in the rate of graft loss or graft function were found between groups 1 and 2 at the end of the follow-up period. Histologically, PTC margination and transplant glomerulopathy were more common in the C4d-positive group, and this difference was statistically significant. There was no statistically significant difference in the degree of plasma cell infiltrates. Conclusions: Unlike in the acute setting, the presence or absence of PTC C4d staining in renal allografts with LAR may not have a predictive value regarding graft outcome.     

Outcome of renal transplantation in fibrillary glomerulonephritis

Fibrillary glomerulonephritis (FGN) is a rare but progressive glomerular disease usually with end-stage renal disease (ESRD) developing within months or few years following the diagnosis. Little is known about the outcome of renal transplantation in patients with ESRD due to FGN. We report four patients with FGN who received renal allografts. Two patients developed recurrent FGN in their grafts. One patient was diagnosed to have recurrent FGN 9 years post-transplant, and lost his graft 4 years thereafter. Another patient had recurrent disease 2 years post-transplant but has stable graft function after 7 years. One patient died with normal renal allograft function 7 years following transplantation. The fourth patient has chronic transplant nephropathy 34 months post-transplant without evidence of recurrent FGN. A literature review revealed 10 additional patients who received 11 renal allografts due to ESRD caused by FGN. Four of these 10 patients had biopsy-proven recurrence (one patient in two subsequent grafts), but this caused graft loss only in 2 patients 56 months and 7 years post-transplant, respectively. The earliest recurrence was diagnosed 2 years post-transplant. We conclude that although the recurrence rate of FGN in renal transplants is high (around 50%), the recurrent disease has a relatively benign course and prolonged graft survival is possible.     

Clinical and Histopathologic Examination of Renal Allografts Treated with Tacrolimus (FK506) for at Least One Year

Background : We clinically and pathologically analyzed renal allografts from 19 renal transplant patients treated with tacrolimus (FK506) for more than 1 year.
Methods : Twenty-six renal allograft biopsy specimens from 19 renal transplant patients who underwent transplantations between 1991 and 1 993 were evaluated. Thirteen biopsies were performed from stable functioning renal allografts with informed consent (nonepisode biopsy) and the other 13 were from dysfunctional renal allografts with a clinical indication for biopsy (episode biopsy).
Results : The main pathologic diagnoses (some overlap) were acute rejection (AR; n = 4), chronic rejection (CR;n = 5), AR + CR(n=4), recurrent IgA nephropathy (n = 5), normal findings (n = 2), minimal-type chronic FK506 nephropathy (n = 9), and mild-type FK506 nephropathy (n = 11). Of the nonepisode biopsies, 7 and 4 biopsies showed minimal-type and mild-type chronic FK506 nephropathy, respectively. Chronic FK506 nephropathy consisted of rough and foamy tubular vacuolization (5 biopsies), arteriolopathy (angio-degeneration of the arteriolar wall; 20 biopsies), focal segmental glomerulosclerosis (4 biopsies) and the striped form of interstitial fibrosis (11 biopsies). The serum creatinine levels of patients in the mild-type chronic FK506 nephropathy group, which included 7 episode biopsies, were statistically higher than those in the minimum-type chronic FK506-nephropathy group (P < 0.001).
Conclusions : This study demonstrates that chronic FK506 nephropathy consists primarily of arteriolopathy manifesting as insudative hyalinosis of the arteriolar wall, and suggests that mild-type chronic FK506 nephropathy is a condition which may lead to deterioration of renal allograft function.     

Successful strategies for renal transplantation in primary oxalosis

Eleven patients, aged 6 months to 47 years, with renal failure due to primary oxalosis, received renal allografts and were followed for 1 to 9 years. A specialized strategy for medical management included intensive pre-transplant hemodialysis and post-transplant long-term diuresis, administration of neutral phosphate, Mg++, and pyridoxine. Seven of ten living-related (LRD) transplants have good renal function, six with no biopsy evidence of renal oxalate deposition at up to 7 years after transplant. Two LRD graft losses from recurrent oxalosis, accompanied by massive secondary oxalate deposits, occurred in patients following endstage renal failure for over 3 years. A third LRD graft loss occurred following long-term (6 month) peritoneal dialysis in an infant. One cadaver transplant recipient has survived with recurrent oxalosis and poor graft function for 9 years. It is possible to perform successful renal transplantation in small children and adults with primary oxalosis and to completely prevent the deposition of oxalate in the renal allograft. Renal transplantation, with a strict medical protocol, would appear to be the initial treatment of choice for renal failure due to primary oxalosis.     

Cholesterol embolization in renal allografts: a clinicopathologic study of 12 cases

Cholesterol embolization (CE) in renal allografts is a rare occurrence, the natural history and prognostic significance of which is poorly characterized. We studied the clinicopathologic features and outcome of the largest known series of CE in renal allografts and combined our cases with those in the literature. We identified renal allograft biopsies with CE from 1997 to September 2004 at University of Pittsburgh Medical Center (UPMC). All pathology material related to such biopsies were examined and correlated with clinical information to determine the most probable CE source. Among 5435 RAB, 19 from 12 cadaveric transplant recipients comprising 7 males and 5 females (median age=63 y) had CE. Donors consisted of 9 males and 2 females (median age=47 y). One donor's age and sex was unknown. The most probable CE source was recipient in 9 cases and donor in 3 cases. Five had acute renal failure without acute cellular rejection and 2 had CE-specific failed allografts. Of 19 RAB, the most frequent coexisting diagnosis was chronic allograft nephropathy (63%). The median follow-up time was 661 days. Combining UPMC and non-UPMC cases (n=37) revealed a statistically significant loss of grafts with donor-derived (P value=0.00459) and early CE (P value=0.00938). In renal allografts, CE most often correlated with recipient and donor atherosclerosis. It may present with acute renal failure, but usually not acute graft loss. Graft failure is significantly associated with donor-derived and early CE. Although its prognosis may be poor in the setting of primary nonfunction, prolonged graft survival may be seen.     

Effects of hypoxia-inducible factor-1alpha expression and C4d deposition in implantation biopsies on renal allograft

Upregulation of hypoxia-inducible factor-1alpha (HIF-1alpha) in response to ischemic states has been suggested to have a role in the development of chronic allograft nephropathy. Deposition of C4d in the peritubular capillaries of renal allografts has been reported to be a sensitive marker of acute humoral rejection. The purpose of this study was to determine the effects of HIF-1alpha expression and C4d deposition in implantation biopsies of renal allografts. Implantation biopsies and 22 rejection proved biopsies were performed in 54 renal transplant recipients between December 1996 and July 1999. The mean follow-up was 82.8 months. Immunohistochemical studies were performed using a mouse monoclonal antibody for HIF-1alpha expression and a rabbit polyclonal antibody for C4d detection. HIF-1alpha was demonstrated in 19 of 54 implantation biopsies (35%), and C4d deposition in one (1.9%). The HIF-1alpha-positive group included a higher percentage of deceased donor organs (66.4% vs 17.1%; P = .002) and longer mean cold ischemia times (261.3 +/- 231 vs 103 +/- 40 min; P = .008) compared with the HIF-1alpha-negative group. The relative risks (95% confidence intervals) of expression of HIF-1alpha for allograft rejection, chronic allograft nephropathy, and graft loss were 1.53 (0.82-2.87), 0.61 (0.06-5.50), and 2.45 (0.62-9.85). The C4d-positive patient developed acute accelerated rejection on postoperative day 4. In the present study, the expression of HIF-1alpha showed a significant correlation with the use of a deceased donor kidney and with cold ischemia time. However, there were no significant effects on the prognosis for a graft after implantation of a kidney with HIF-1alpha expression.     

Reproducibility of the Banff schema in reporting protocol biopsies of stable renal allografts.

BACKGROUND: There is evidence that biopsy of stable renal allografts may be of value in predicting chronic allograft nephropathy, the main cause of graft loss. However, the reproducibility of such histological evaluation has not been tested in this setting. We tested the reproducibility of the Banff schema for this purpose. METHODS: We rated acute and chronic changes in 184 protocol biopsies. Individual pathologists at two different Canadian transplant centres reported independently. RESULTS: There was agreement in 73.53, 42.86, and 77.08% of cases in assigning a diagnosis of acute rejection, borderline changes (as defined in the schema), and no acute rejection, respectively. Applying kappa statistics, there was very good agreement in making the diagnosis of acute rejection vs no acute rejection (kappa 0.77). There was good inter-observer agreement in scoring glomerulitis, intimal arteritis, interstitial infiltrates, tubulitis, and arteriolar hyalinosis. Rating chronic changes also gave good inter-observer agreement (kappa=0.53, 0.65, and 0.62, respectively, for mild, moderate, and severe chronic allograft nephropathy). Agreement on transplant glomerulopathy was, however, poor. CONCLUSIONS: We conclude that the Banff classification provides a reproducible method for the histological assessment of protocol renal allograft biopsies in stable grafts. Such biopsies may be valuable in detecting subclinical rejection and early chronic allograft nephropathy and may also be used as surrogate end-points in the evaluation of therapy to prevent the latter.     

Chronic renal allograft nephropathy

Chronic rejection/chronic allograft nephropathy is the most prevalent cause of renal graft loss after the first year post-transplant. Chronic rejection/chronic allograft nephropathy is characterized by a slow progressive deterioration of graft function, often in combination with proteinuria and hypertension. Both immunologic and non-immunologic factors play key roles in the pathogenesis of chronic allograft nephropathy. Acute rejection episodes are the most prevalent risk factor for chronic rejection. Many risk factors for chronic allograft nephropathy have been identified, such as delayed graft function, nephron-dosing mismatch, repeated acute rejection episodes, and pathologically severe rejection. However, the precise pathogenesis of chronic allograft nephropathy remains elusive. The differential diagnosis of immunologically mediated chronic rejection and chronic rejection caused by non-immunologic factors is usually not possible using clinical parameters. The histopathologic findings of chronic allograft nephropathy are progressive interstitial fibrosis and remodelling of the vascular wall, and these findings are nonspecific. However, typical chronic transplant glomerulopathy, which affects glomerular tufts, as well as the multilayering of the peritubular capillary basement membrane, are characteristic of immunologic chronic rejection. Furthermore, in long-surviving patient with an allograft treated with a potent immunosuppressive agent, a calcineurin inhibitor, two or more concomitant independent lesions often develop. Therefore, the term "chronic allograft nephropathy" may be clinically preferable to "chronic rejection" to describe the gradual decline in graft function months or years after transplantation, in the absence of a well defined mechanism of graft dysfunction. The most effective way to prevent chronic allograft nephropathy is to avoid any kind of graft damage via either immunologic or non-immunologic mechanisms. Received: April 1, 2000 / Accepted: May 2, 2000     

Longitudinal analysis of chronic allograft nephropathy: clinicopathologic correlations

BACKGROUND: Loss of the allograft from chronic allograft nephropathy and death of the patient from vascular, malignant, or infective disease are the major problems in renal transplantation today. Protocol biopsy of the long-term kidney has provided new data with which to develop strategies for prevention and treatment of chronic allograft nephropathy. METHODS: Two series of long-term protocol biopsies are reviewed. In the first, renal biopsies were obtained at time 0, and at 3 months and 12 months, and the recipients of the renal allografts were followed up for up to 15 years. In the second, the kidneys of recipients of simultaneous pancreas kidney transplants were biopsied annually for 10 years, and the results correlated with clinical events. RESULTS: Chronic allograft nephropathy is caused by acute and chronic immune-mediated damage, as well as by chronic calcineurin inhibitor nephrotoxicity. Both immune and nonimmune mechanisms exacerbate pre-existing donor disease and ischemia-reperfusion injury. Established interstitial fibrosis and arteriolar hyalinosis lead to progressive glomerular sclerosis and eventual loss of the graft. CONCLUSION: Protocol biopsies have shown that clinical parameters of renal function underestimate the severity of chronic graft damage. Strategies for preventing or treating chronic renal allograft dysfunction and subsequent graft loss must better control rejection and simultaneously avoid nephrotoxicity.     

Impaired renal allograft function: a comparative study with angiography and histopathology.

We reviewed 47 renal transplant recipients who had undergone angiography and transplant biopsy to evaluate impaired allograft function. Angiographic criteria for rejection were seen in all allografts with hyperacute rejection, accelerated rejection and chronic rejection, and in 13 of 17 allografts with acute cellular rejection. Angiography was normal in allografts with vasomotor nephropathy or transplant glomerulopathy. Angiography is an accurate method for the diagnosis of most causes of post-transplant dysfunction.     

Glomerulonephritis is the major cause of proteinuria in renal transplant recipients: histopathologic findings of renal allografts with proteinuria

The proteinuria in renal allograft recipients has been regarded as a sign of poor prognosis. The causes of post-transplant proteinuria include chronic rejection, chronic transplant glomerulopathy, glomerulonephritis (GN), acute rejection, and cyclosporine nephrotoxicity. Among them, chronic rejection is known to be most frequent. We analyzed the histopathologic findings of renal allograft biopsies in 197 Korean recipients with proteinuria. Among them, 26 patients developed proteinuria over 500 mg/d. All patients received baseline immunosuppression with cyclosporine. From 26 patients with post-transplant proteinuria, 29 biopsies were performed and their histologic diagnoses were immunoglobulin A nephropathy (IgAN) in 17, IgAN combined with chronic allograft nephropathy in 1, focal segmental glomerulosclerosis in 2, crescentic GN in 1, membranous GN in 1, diabetic nephropathy in 1, acute tubulointerstitial nephritis in 1, and chronic rejection in 3 biopsies. The remaining two biopsies showed nonspecific findings. The most common cause of post-transplant proteinuria was IgAN (62% of biopsies). The incidence of chronic rejection was relatively low and predominant cyclosporine-associated changes were not observed. In conclusion, our data suggest that the main causes of post-transplant proteinuria in Korea are primary glomerulonephritides rather than chronic rejection or cyclosporine nephrotoxicity, and the kidney allograft biopsies from patients with proteinuria should be handled as native kidney.     

Polyomavirus nephropathy after renal transplantation: a single centre experience

BACKGROUND: Polyomavirus associated nephropathy (PVN) in renal transplant recipients has been observed with increasing frequency recently and has emerged as a cause of allograft failure linked to highly potent new immunosuppressive regimens containing tacrolimus or mycophenolate mofetil (MMF). METHODS: Polyomavirus associated nephropathy was identified in nine out of 182 patients who received renal transplantation between October 1998 and July 2003. PVN was confirmed by allograft biopsy. The clinical records of these nine patients were reviewed, as were all of the allograft biopsies. Electron microscopy was performed in all nine cases. After the diagnosis of PVN, maintenance immunosuppression was reduced. The clinical course and outcome of the PVN patients were reviewed in relation to manipulation of immunosuppressive agents. RESULTS: There were nine cases of PVN in renal transplant recipients and the incidence of PVN was 4.9%. All patients with PVN were under triple immunosuppression comprising tacrolimus and MMF. The mean time to a diagnosis of PVN was 7.8 months after transplantation. Three of the nine patients received antirejection therapy prior to PVN. Seven out of nine PVN patients presenting acute allograft dysfunction were initially treated with high-dose intravenous steroid pulse or OKT3 before reduction of the immunosuppression. After reduction of the immunosuppression, seven patients stabilized their renal function. Two (22%) lost their grafts due to persistent PVN and chronic rejection. Two (22%) patients later developed acute rejection after reduction of the immunosuppression. CONCLUSION: PVN can cause allograft dysfunction and graft loss. Renal allograft recipients who are at risk of PVN should be routinely screened with urine cytology and quantitative measurements of viral load in the blood, particularly patients who had graft dysfunction. Early diagnosis and judicious alteration of immunosuppressive agents might permit a superior prognosis and reduce the graft loss from PVN in renal transplant recipients.     

Chronic allograft nephropathy: An update.

Chronic allograft nephropathy is the most prevalent cause of renal transplant failure in the first post-transplant decade, but its pathogenesis has remained elusive. Clinically, it is characterized by a slow but variable loss of function, often in combination with proteinuria and hypertension. The histopathology is also not specific, but transplant glomerulopathy and multilayering of the peritubular capillaries are highly characteristic. Several risk factors have been identified, such as advanced donor age, delayed graft function, repeated acute rejection episodes, vascular rejection episodes, and rejections that occur late after transplantation. A common feature of chronic allograft nephropathy is that it develops in grafts that have undergone previous damage, although the mechanism(s) responsible for the progressive fibrosis and tissue remodeling has not yet been defined. Hypotheses to explain chronic allograft nephropathy include the immunolymphatic theory, the cytokine excess theory, the loss of supporting architecture theory, and the premature senescence theory. The most effective option to prevent chronic allograft nephropathy is to avoid graft injury from both immune and nonimmune mechanisms.     

Posttransplant recurrence of calcium oxalate crystals in patients with primary hyperoxaluria: Incidence,risk factors,and effect on renal allograft function

Primary hyperoxaluria (PH) is a metabolic defect that results in oxalate overproduction by the liver and leads to kidney failure due to oxalate nephropathy. As oxalate tissue stores are mobilized after transplantation, the transplanted kidney is at risk of recurrent disease. We evaluated surveillance kidney transplant biopsies for recurrent calcium oxalate (CaOx) deposits in 37 kidney transplants (29 simultaneous kidney and liver [K/L] transplants and eight kidney alone [K]) in 36 PH patients and 62 comparison transplants. Median follow-up posttransplant was 9.2 years (IQR: [5.3, 15.1]). The recurrence of CaOx crystals in surveillance biopsies in PH at any time posttransplant was 46% overall (41% in K/L, 62% in K). Higher CaOx crystal index (which accounted for biopsy sample size) was associated with higher plasma and urine oxalate following transplant (p < .01 and p < .02, respectively). There was a trend toward higher graft failure among PH patients with CaOx crystals on surveillance biopsies compared with those without (HR 4.43 [0.88, 22.35], p = .07). CaOx crystal deposition is frequent in kidney transplants in PH patients. The avoidance of high plasma oxalate and reduction of CaOx crystallization may decrease the risk of recurrent oxalate nephropathy following kidney transplantation in patients with PH. This study was approved by the IRB at Mayo Clinic.     

Recurrent 2,8‐Dihydroxyadenine Nephropathy: A Rare but Preventable Cause of Renal Allograft Failure

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive enzyme defect of purine metabolism that usually manifests as 2,8‐dihydroxyadenine (2,8‐DHA) nephrolithiasis and more rarely chronic kidney disease. The disease is most often misdiagnosed and can recur in the renal allograft. We analyzed nine patients with recurrent 2,8‐DHA crystalline nephropathy, in all of whom the diagnosis had been missed prior to renal transplantation. The diagnosis was established at a median of 5 (range 1.5–312) weeks following the transplant procedure. Patients had delayed graft function (n = 2), acute‐on‐chronic (n = 5) or acute (n = 1) allograft dysfunction, whereas one patient had normal graft function at the time of diagnosis. Analysis of allograft biopsies showed birefringent 2,8‐DHA crystals in renal tubular lumens, within tubular epithelial cells and interstitium. Fourier transformed infrared microscopy confirmed the diagnosis in all cases, which was further supported by 2,8‐DHA crystalluria, undetectable erythrocyte APRT enzyme activity, and genetic testing. With allopurinol therapy, the allograft function improved (n = 7), remained stable (n = 1) or worsened (n = 1). At last follow‐up, two patients had experienced allograft loss and five had persistent chronic allograft dysfunction. 2,8‐DHA nephropathy is a rare but underdiagnosed and preventable disorder that can recur in the renal allograft and may lead to allograft loss.     

The Remission of Post-Transplant Nephrotic Syndrome Clinicopathologic Characterization

Among 67 renal transplant recipients with nephrotic syndrome (NS), nine episodes were reversible in eight patients. Biopsies showed minimal-change disease, focal segmental membranous glomerulonephritis and acute glomerulitis, IgA nephropathy and acute glomerulitis or thrombotic microangiopathy, and chronic transplant nephropathy with or without acute glomerulitis. NS developed 1-4 months post transplant in the four patients with minimal-change disease, but later (33-151 months) in the others. At onset, serum creatinine was normal or elevated. Treatment included calcium-channel blockers, angiotensin-converting enzyme inhibitors, or both, together with routine antirejection therapy. Remission was achieved 4-12 months after onset, when renal function remained normal in four, improved in four, and worsened in one. At last follow-up, six patients still had remission and functional grafts. One lost graft to chronic transplant nephropathy while NS remained in remission. In the remaining patient, proteinuria, which was due to chronic transplant glomerulopathy unrelated to the initial minimal-change disease-associated NS, recurred 50 months post transplant. Remission of post-transplant NS is possible. It is often associated with minimal-change diseases and less frequently with other glomerular lesions, including acute glomerulitis. Reversible post-transplant NS does not have an adverse effect on the renal allografts.