Renal Transplant Biopsies Research Articles

IgA1 dominant subclass of latent IgA mesangial deposition in donated kidney.

BackgroundIn the pathogenesis of immunoglobulin A nephropathy (IgAN), the IgA1 subclass is more important than the IgA2 subclass. In healthy men, the prevalence of mesangial IgA deposition has been previously investigated. However, it remains unknown whether the presence of urinary abnormalities depends on the subclass of IgA deposition.Materials and methodsWe researched the subclasses of IgA (IgA1 and IgA2) by the direct immunofluorescence (IF) staining method using specimens in which we identified the deposition of IgA through zero-hour renal transplant biopsies from donors without urinary abnormalities. The samples of the zero-hour biopsies were collected from 46 cases of living renal transplant patients at Nishinomiya Hospital, Hyogo Prefecture, from January 2011 to December 2013.ResultsIn seven of the 46 cases (15%), IgA deposition and C3 in mesangium were confirmed. All seven cases showed IgA1 predominant mesangial deposition on IF. The results of the histological evaluations for all seven cases were Oxford Classification M0.S0.E0.T0.ConclusionThis study showed similar patterns of latent mesangial IgA deposition according to IgA subclass and frequency of C3 deposition as IgAN. Latent mesangial IgA deposition may require some, as yet undefined factors, to become clinically apparent as IgAN.

Plasma-cell-rich infiltrates in paediatric renal transplant biopsies are associated with increased risk of renal allograft failure.

Increased plasma cell infiltration in renal allograft biopsies is a rare finding associated with poor outcome in adult renal transplant recipients. The clinical impact of increased plasma cell infiltrates in paediatric renal transplant recipients (pRTR) remains unknown. We conducted a retrospective case-control study from April 1996 to March 2014 comparing the outcome of pRTR with increased (>10% of infiltrate) plasma cells in renal transplant biopsies to a control cohort of pRTR without increased plasma cell infiltration but similar grade of rejection according to Banff classification. Increased plasma cell infiltrates were present in 14 of 162 (9%) reviewed pRTR aged 3.2-17.5 (median 13.4) years at time of transplantation. Compared with 14 pRTR renal transplant biopsies without significantly increased plasma cells, there were no significant differences in mismatch and baseline estimated glomerular filtration rate (eGFR). Plasma cells were present in case biopsies at a maximal density of 14-116 (median 33) plasma cells/HPF. Increased plasma cells were associated with decreased eGFR at biopsy (22 vs. 49ml/min/1.73m2; p < 0.001) and 4weeks post-biopsy (26 vs. 56ml/min/1.73m2; p < 0.001) despite comparable eGFR 4 weeks prior to biopsy. Increased plasma cells were further associated with significantly increased frequency of renal allograft loss (71% vs. 7%; p < 0.001) at 0-27 (median 2) months after biopsy. Increased plasma cell infiltrates in pRTR are uncommon but associated with significantly reduced renal allograft survival as well as significantly reduced allograft function in surviving grafts.

Lysosomal protease cathepsin D; a new driver of apoptosis during acute kidney injury.

Acute kidney injury (AKI) is an abrupt reduction in kidney function caused by different pathological processes. It is associated with a significant morbidity and mortality in the acute phase and an increased risk of developing End Stage Renal Disease. Despite the progress in the management of the disease, mortality rates in the last five decades remain unchanged at around 50%. Therefore there is an urgent need to find new therapeutic strategies to treat AKI. Lysosomal proteases, particularly Cathepsin D (CtsD), play multiple roles in apoptosis however, their role in AKI is still unknown. Here we describe a novel role for CtsD in AKI. CtsD expression was upregulated in damaged tubular cells in nephrotoxic and ischemia reperfusion (IRI) induced AKI. CtsD inhibition using Pepstatin A led to an improvement in kidney function, a reduction in apoptosis and a decrease in tubular cell damage in kidneys with nephrotoxic or IRI induced AKI. Pepstatin A treatment slowed interstitial fibrosis progression following IRI induced AKI. Renal transplant biopsies with acute tubular necrosis demonstrated high levels of CtsD in damaged tubular cells. These results support a role for CtsD in apoptosis during AKI opening new avenues for the treatment of AKI by targeting lysosomal proteases.

Implementation and Results of a Percutaneous Renal Allograft Biopsy Protocol to Reduce Complication Rate

Percutaneous renal transplant biopsy (PRTB) is the gold standard for evaluating allograft rejection after renal transplant. Hemorrhage is the predominant complication. We describe the implementation of a standardized protocol for PRTB at a single institution, with the aim of reducing bleeding complications. Utilizing the plan-do-study-act model for quality improvement, we created and deployed a protocol centered on controlling patient’s hypertension, platelet function, and anticoagulation status. The 4-year study encompassed a total of 880 PRTBs, before and after implementation of the protocol. Total complication rate, which was 5.8% in the 2 years leading up to implementation of the protocol, was reduced to 2.9% after the protocol was introduced (P = .04). A standardized approach to PRTB can potentially lower complication rates; we present a framework for implementating a quality improvement protocol at other institutions.

Nature, timing, and severity of complications from ultrasound-guided percutaneous renal transplant biopsy.

We sought to review our kidney transplant biopsy experience to assess the incidence, type, presenting symptoms, and timing of renal transplant biopsy complications, as well as determine any modifiable risk factors for postbiopsy complications. This is an observational analysis of patients at the University of Wisconsin between January 1, 2000, and December 31, 2009. Patients with an INR ≥1.5 or platelet counts less than 50000 were not biopsied. An 18-gauge needle was used for biopsy. Over the study period, 3738 biopsies were performed with 66 complications (1.8%). No deaths occurred. A total of 0.7% were mild complications, 0.7% were moderate complications, 0.21% were severe complications, and 0.19% were life-threatening. Most complications occurred within the 4-h postbiopsy period, although serious complications were often delayed: 67% of complications requiring surgical intervention presented greater than 4h after biopsy. Biopsy within 1week of transplant had a 311% increased risk of a complication. Postbiopsy reduction in hematocrit and hemoglobin at 4h was associated with a complication. In conclusion, life-threatening complications after renal allograft biopsy occurred in 0.19% of patients. Most complications occurred within 4h postprocedure; however, many serious complications occurred with a time delay after initially uneventful monitoring. The only clinically significant laboratory predictor of a complication was a fall in the hematocrit or hemoglobin within 4h. Patients biopsied within a week of transplant were at the highest risk for a complication and should therefore be most closely monitored.

Percutaneous renal transplant biopsy: is the safety profile adequate for short-term postprocedure monitoring?

Percutaneous renal transplant biopsy: is the safety profile adequate for short-term postprocedure monitoring?

Endothelial activation, lymphangiogenesis, and humoral rejection of kidney transplants

Antibody-mediated rejection (ABMR) is implicated in 45% of renal allograft failure and 57% of late allograft dysfunction. Peritubular capillary C4d is a specific but insensitive marker of ABMR. The 2013 Banff Conference ABMR revised criteria included C4d-negative ABMR with evidence of endothelial-antibody interaction. We hypothesized that endothelial activation and lymphangiogenesis are increased with C4d-negative ABMR and correlate with intragraft T-regulatory cells and T-helper 17. Seventy-four renal transplant biopsies were selected to include (a) ABMR with C4d Banff scores ≥2 (n = 35), (b) variable microvascular injury and C4d score 0-1 (n = 24), and (c) variable microvascular injury and C4d score = 0 (n = 15). Controls included normal preimplantation donor kidneys (n = 5). Immunohistochemistry for endothelial activation (P- and E-selectins [SEL]), lymphangiogenesis (D2-40), T-regulatory cells (FOXP3), and T-helper 17 (STAT3) was performed. Microvessel and inflammatory infiltrate density was assessed morphometrically in interstitium and peritubular capillaries. All transplants had significantly higher microvessel and lymph vessel density compared with normal. Increased expression of markers of endothelial activation predicted transplant glomerulopathy (P-SEL, P = .003). Increased P-SEL and D2-40 were associated with longer interval from transplant to biopsy (P = .005). All 3 markers were associated with increased interstitial fibrosis, tubular atrophy, and graft failure (P-SEL, P < .001; E-SEL, P = .0011; D2-40, P = .012). There was no association with the intragraft FOXP3/STAT3 ratio. We conclude that endothelial activation and lymphangiogenesis could represent a late response to injury leading to fibrosis and progression of kidney damage, and are independent of the intragraft FOXP3/STAT3 ratio. Our findings support the therapeutic potential of specifically targeting endothelial activation.

Gastric bypass oxalosis in renal transplant: clinicopathologic correlates

Background: Reports of oxalate nephropathy after gastric bypass (GB) leading to graft loss of kidneys causes concern for transplant professionals. We examined the clinical phenotype of GB related oxalate nephropathy (ON), its contribution to graft loss and propose a management strategy to mitigate graft loss in renal transplant recipients. Methods: Retrospective case series of patients who had GB surgery prior to renal transplant at a single institution were studied. Oxalate burden in renal transplant biopsies was quantified by intratubular calcium/glomeruli (Ca T/G) ratio and correlated with other clinical covariates. Results: We identified 16 GB patients; the mean BMI pre-GB was 52.5 kg/m2 (range 42-80), with a follow-up BMI of 30.9 kg/m2 (range 22-36.5) at transplant evaluation. Among 11 patients who had for cause biopsies, 3 patients had significant intra tubular allograft calcium oxalate deposition with a median time from graft to failure of 9 months. Among patients with functioning grafts, follow up creatinine averaged 1.6 mg/dl (0.9-3.4 mg/dl); median follow up was 4 years (0.5-7 years). Conclusions: The relationship between GB and ON post renal transplant is variable. The expression of ON after acute kidney injury (AKI) suggests that mitigating strategies should be directed at preventing alloimmune and other forms of AKI in addition to managing oxalate intake.

Tubuloreticular Inclusions in Renal Allografts Associate with Viral Infections and Donor-Specific Antibodies.

The presence of tubuloreticular inclusions (TRIs) in native glomerular endothelial cells associates with viral infections and lupus nephritis. However, the associations of TRIs in renal transplant biopsy specimens are not known. We analyzed data from 316 patients who had a transplant biopsy with electron microscopy examination; 41 of 316 (13.0%) patients had TRIs. Patients with TRIs had significantly lower allograft survival rates (50.9%) than patients without TRIs (74.3%; P=0.03). Transplant glomerulopathy-free survival was also inferior in the TRI-positive group (57.5%) compared with the TRI-negative group (87.3%; P=0.002). Serologically, hepatitis C associated with the presence of TRIs (P=0.04) along with donor-specific antibodies (P=0.01). Furthermore, patients who were TRI positive were more likely than patients who were TRI negative to have had a previous rejection episode (P=0.02). On multivariate analysis, TRIs associated with prior rejection, viral infections, and class 1 HLA donor-specific antibodies. These results show that the presence of TRIs in renal allograft biopsy specimens associates with poor allograft outcomes and serologic evidence of viral infections and alloimmunity. The association with alloimmunity is a novel finding that warrants additional investigation.

Granulomatous interstitial nephritis: a chameleon in a globalized world.

Two articles in this issue deal with granulomatous acute interstitial nephritis (GIN), a rare disorder seen in 0.5–0.9% of native and 0.6% of transplant renal biopsies [1]. In the first article, Agrawal and co-workers report 10 years of experience with GIN in a tertiary centre in India [2]. In contrast to the experience from Western countries, tuberculosis accounted for more than half of cases. The authors emphasize the challenge of making the diagnosis and recommend a high degree of suspicion [2]. In a second article, Shah and colleagues from the USA [3] review GIN and also highlight current challenges in describing the interesting case of a 69-year-old man with GIN ascribed to doxycycline in whom a positive quantiferon test was received and who eventually died from multi-organ failure. Without autopsy we will never know whether he actually had tuberculosis but their case also reminds us that even with sophisticated testing the cause of GIN remains unclear in a proportion of patients. In this comment, we reflect on both articles and provide some context with an emphasis on pathology and disease patterns worldwide, pitfalls and the diagnostic approach in clinic.

Use of Quantitative Real Time Polymerase Chain Reaction to Assess Gene Transcripts Associated With Antibody-Mediated Rejection of Kidney Transplants.

Microarray studies have shown elevated transcript levels of endothelial and natural killer (NK) cell-associated genes during antibody-mediated rejection (AMR) of the renal allograft. This study aimed to assess the use of quantitative real-time polymerase chain reaction as an alternative to microarray analysis on a subset of these elevated genes. Thirty-nine renal transplant biopsies from patients with de novo donor-specific antibodies and eighteen 1-year surveillance biopsies with no histological evidence of rejection were analyzed for expression of 11 genes previously identified as elevated in AMR. Expression levels of natural killer markers were correlated to microcirculation inflammation and graft outcomes to a greater extent than endothelial markers. Creating a predictive model reduced the number of gene transcripts to be assessed to 2, SH2D1b and MYBL1, resulting in 66.7% sensitivity and 89.7% specificity for graft loss. This work demonstrates that elevated gene expression levels, proposed to be associated with AMR, can be detected by established quantitative real-time polymerase chain reaction technology, making transition to the clinical setting feasible. Transcript analysis provides additional diagnostic information to the classification schema for AMR diagnosis but it remains to be determined whether significant numbers of centres will validate transcript analysis in their laboratories and put such analysis into clinical use.

Transplant biopsy beyond light microscopy.

Despite its long-standing status as the diagnostic “gold standard”, the renal transplant biopsy is limited by a fundamental dependence on descriptive, empirically-derived consensus classification. The recent shift towards personalized medicine has resulted in an increased demand for precise, mechanism-based diagnoses, which is not fully met by the contemporary transplantation pathology standard of care. The expectation is that molecular techniques will provide novel pathogenetic insights that will allow for the identification of more accurate diagnostic, prognostic, and therapeutic targets. Here we review the current state of molecular renal transplantation pathology. Despite significant research activity and progress within the field, routine adoption of clinical molecular testing has not yet been achieved. The recent development of novel molecular platforms suitable for use with formalin-fixed paraffin-embedded tissue will offer potential solution for the major barriers to implementation. The recent incorporation of molecular diagnostic criteria into the 2013 Banff classification is a reflection of progress made and future directions in the area of molecular transplantation pathology. Transcripts related to endothelial injury and NK cell activation have consistently been shown to be associated with antibody-mediated rejection. Prospective multicenter validation and implementation of molecular diagnostics for major entities remains an unmet clinical need in transplantation. It is expected that an integrated system of transplantation pathology diagnosis comprising molecular, morphological, serological, and clinical variables will ultimately provide the greatest diagnostic precision.

Interpreting CD56+ and CD163+ Infiltrates in Early versus Late Renal Transplant Biopsies

Background: CD56+ and CD163+ cell infiltration in human kidney transplant biopsies have not been fully evaluated. Methods: We investigated the association of CD56+ and CD163+ cell infiltration with human kidney transplant biopsies with antibody- or T-cell-mediated rejection (TCMR) and other histologic lesions. One hundred and seventy four clinically indicated transplant biopsies were included in this analysis. Immunohistochemical staining for C4d, CD56 and CD163 was performed. Results: One hundred and seventy four indication biopsies were divided into early (≤1 year posttransplant; n = 49) and late (>1 year posttransplant; n = 125) biopsies. High numbers of CD56+ cells were uncommon in early biopsies except for those with antibody-mediated rejection (AMR) only. On the other hand, high numbers of CD56+ cells were observed in late biopsies diagnosed as TCMR only, AMR only, and TCMR combined with AMR. In early biopsies, both CD56+ and CD163+ infiltrates correlated strongly with interstitial inflammation, tubulitis, and peritubular capillaritis (ptc) scores. The ci and ct scores, however, were correlated only with the number of CD56+ cells. In late biopsies, on the other hand, the number of CD56+ infiltrates was correlated only with ptc, while the number of CD163+ infiltrates was weakly correlated with any histologic lesion. Multivariable analyses showed that chronic active AMR and the number of CD56+ cells/10 HPF were independently associated with death-censored graft failure post-biopsy. The number of CD163+ cells was not correlated with any pathologic lesion and post-biopsy graft failure. CD56+ infiltrates were also associated with interstitial fibrosis and tubular atrophy. Conclusions: Intragraft CD56+ cell infiltrates were significantly associated with AMR and subsequent poor clinical outcomes.

BK polyomavirus-infected nephrogenic adenoma of the urinary bladder in a renal transplant recipient: A case report

This report describes the morphological and immunohistochemical features of the first case of a nephrogenic adenoma (NA) of the urinary bladder infected with polyomavirus. The findings occurred in a female patient, 6 months post cadaveric renal transplant. Voided urine cytology was positive for decoy cells. Renal transplant biopsy showed no evidence of BKV allograft nephropathy. Cystoscopy demonstrated multiple erythematous patchy and nodular areas. These were found in the left and right posterior wall, and the right lateral wall toward the bladder neck, and were suspicious for either chronic inflammation or neoplasia.Hematoxylin–eosin stained sections showed a NA with scattered pleomorphic nuclei demonstrating smudged chromatin and amorphous basophilic ground glass inclusions. Strong expression of polyomavirus large T antigen (SV40) and VP1 was seen in atypical lesional cells, consistent with cytopathic lytic polyomavirus infection. Positive staining with PAX8 supports the renal cell derivation of NA. The findings in the present case suggest that polyomavirus infection, as an irritant of the bladder mucosa, contributed to the cytologic atypia of infected lesional cells but is not a pathogenic factor of NA.

The role of electron microscopy in renal allograft biopsy evaluation.

To review and discuss the use of electron microscopy in the examination of renal transplant biopsies, in particular its role in the diagnosis of glomerular disease and antibody-mediated rejection. Electron microscopy can detect recurrent and de-novo glomerular disease at early stages, in particular for focal and segmental glomerulosclerosis and thrombotic microangiopathy.Ultrastructural features are an integral part of the Banff definition of chronic, active antibody-mediated rejection, which has been recently modified to include ultrastructural-only glomerular double contours. In addition, the threshold of peritubular capillary basement membrane multilayering diagnostic for chronic, active antibody-mediated rejection has been changed. As an area for further investigation, ultrastructural-only glomerular and peritubular capillary features could become tools in the early detection of antibody-mediated rejection. Electron microscopy is important in the diagnosis of glomerular disease and chronic, active antibody-mediated rejection, both of which contribute to late graft loss. Early detection and treatment may help prolong graft survival. More data are needed on the early ultrastructural features of antibody-mediated injury, so that the usefulness of this technique can be compared with emerging technologies such as transcript analysis.

Markers of Endothelial-to-Mesenchymal Transition: Evidence for Antibody-Endothelium Interaction during Antibody-Mediated Rejection in Kidney Recipients.

Antibody-mediated rejection (ABMR) is a leading cause of allograft loss. Treatment efficacy depends on accurate diagnosis at an early stage. However, sensitive and reliable markers of antibody-endothelium interaction during ABMR are not available for routine use. Using immunohistochemistry, we retrospectively studied the diagnostic value of three markers of endothelial-to-mesenchymal transition (EndMT), fascin1, vimentin, and heat shock protein 47, for ABMR in 53 renal transplant biopsy specimens, including 20 ABMR specimens, 24 cell-mediated rejection specimens, and nine normal grafts. We validated our results in an independent set of 74 unselected biopsy specimens. Endothelial cells of the peritubular capillaries in grafts with ABMR expressed fascin1, vimentin, and heat shock protein 47 strongly, whereas those from normal renal grafts did not. The level of EndMT marker expression was significantly associated with current ABMR criteria, including capillaritis, glomerulitis, peritubular capillary C4d deposition, and donor-specific antibodies. These markers allowed us to identify C4d-negative ABMR and to predict late occurrence of disease. EndMT markers were more specific than capillaritis for the diagnosis and prognosis of ABMR and predicted late (up to 4 years after biopsy) renal graft dysfunction and proteinuria. In the independent set of 74 renal graft biopsy specimens, the EndMT markers for the diagnosis of ABMR had a sensitivity of 100% and a specificity of 85%. Fascin1 expression in peritubular capillaries was also induced in a rat model of ABMR. In conclusion, EndMT markers are a sensitive and reliable diagnostic tool for detecting endothelial activation during ABMR and predicting late loss of allograft function.

G486(P) First successful paediatric hla incompatible renal transplantation in the united kingdom

Aims To report the successful outcome of HLA incompatible renal transplantation using plasmapheresis and intravenous immunoglobulin (on day –1) and quadruple immunosuppression with anti–thymocyte globulin (1.5 mg/kg day 1–4), corticosteroids, mycophenolate mofetil and tacrolimus (from day -7). Methods Six month follow–up data of 14–year old young lady who underwent living related ABO compatible (O into B) and HLA incompatible renal transplantation from her father (mismatch 0,1,1) for end-stage kidney disease on peritoneal dialysis secondary to congenital abnormalities of the kidney and urinary tract with bilateral renal dysplasia, recurrent urinary tract infections, bilateral vesico–ureteric reflux after left ureteric reimplantation and right nephrectomy. She had a previous failed renal transplantation at 11 years of age with primary non–function due to intra-renal thrombosis (no acute rejection or TMA) requiring transplant nephrectomy the day after transplantation with 95–100% calculated reaction frequency due to HLA antibodies, specific for mismatches HLA B7 and DQ8 against father with B cell positive (T cell negative) crossmatch which was reduced to negative with test plasma exchange and reduction in MFI from 16,200 to 6,480 and from 11,602 to 4,625 on the day prior to transplantation. She had no offers from the deceased donor waiting list or via the paired exchange scheme (NLDKSS). Results Successful renal transplant without further antibody removal or surgical complications with six month follow–up data with stable renal allograft function with eGFR of 60–96 mls/min/1.73m 2 , 12-hour trough tacrolimus and mycophenolate levels of 7.3 mcg/l and 3.0 mg/l respectively, controlled hypertension on one anti-hypertensive agent with minimal albuminuria (17.4 mg/mmol). Her DSA reduced to 4,691on day 2 but increased further to 23,772 to 38,630 during weeks 1 to 3 and have stabilised out at 21,246 to 22,168 (B7 and DQ8 of 8,407 and 13,761 respectively). She has had three percutaneous renal transplant biopsies at weeks 2, 7 and 11 without acute rejection or IFTA but moderate concentric fibrous intimal thickening of large muscular arteries and C4d deposition in peritubular capillaries and glomeruli. Conclusions This is the first paediatric HLA incompatible renal transplantation in UK and highlights that clinicians must consider this option in ESKD patients whose living donors have been excluded due to HLA incompatibility.

Proximal Tubular Injury in Medullary Rays Is an Early Sign of Acute Tacrolimus Nephrotoxicity.

Tacrolimus (FK506) is one of the principal immunosuppressive agents used after solid organ transplantations to prevent allograft rejection. Chronic renal injury induced by tacrolimus is characterized by linear fibrosis in the medullary rays; however, the early morphologic findings of acute tacrolimus nephrotoxicity are not well characterized. Kidney injury molecule-1 (KIM-1) is a specific injury biomarker that has been proven to be useful in the diagnosis of mild to severe acute tubular injury on renal biopsies. This study was motivated by a patient with acute kidney injury associated with elevated serum tacrolimus levels in whom KIM-1 staining was present only in proximal tubules located in the medullary rays in the setting of otherwise normal light, immunofluorescent, and electron microscopy. We subsequently evaluated KIM-1 expression in 45 protocol and 39 indicated renal transplant biopsies to determine whether higher serum levels of tacrolimus were associated with acute segment specific injury to the proximal tubule, as reflected by KIM-1 staining in the proximal tubules of the cortical medullary rays. The data suggest that tacrolimus toxicity preferentially affects proximal tubules in medullary rays and that this targeted injury is a precursor lesion for the linear fibrosis seen in chronic tacrolimus toxicity.

Biopsy Induced Arteriovenous Fistula and Venous Stenosis in a Renal Transplant

Renal transplant vein stenosis is a rare cause of allograft dysfunction. Percutaneous stenting appears to be safe and effective treatment for this condition. A 56-year-old Caucasian female with end stage renal disease received a deceased donor renal transplant. After transplant, her serum creatinine improved to a nadir of 1.2 mg/dL. During the third posttransplant month, her serum creatinine increased to 2.2 mg/dL. Renal transplant biopsy showed BK nephropathy. Mycophenolate was discontinued. Over the next 2 months, her serum creatinine crept up to 6.2 mg/dL. BK viremia improved from 36464 copies/mL to 15398 copies/mL. A renal transplant ultrasound showed lower pole arteriovenous fistula and abnormal waveforms in the renal vein. Carbon dioxide (CO2) angiography demonstrated severe stenosis of the transplant renal vein. Successful coil occlusion of fistula was performed along with angioplasty and deployment of stent in the renal transplant vein. Serum creatinine improved to 1.5 mg/dL after.

Desmopressin use prior to renal transplant biopsy-does it fit?

Desmopressin acetate (DDAVP), a selective agonist of type 2 vasopressin receptors, is sometimes used prior to percutaneous renal biopsy to reduce the risk of bleeding complications. DDAVP increases free water reabsorption in renal collecting ducts, potentially leading to water intoxication or dilutional hyponatraemia. We present two cases, where DDAVP was used prior to percutaneous renal transplant biopsy and was associated with severe hyponatraemia and neurological sequelae. With DDAVP being advocated in many centres prior to percutaneous renal biopsy, these cases highlight the need for increased awareness regarding side effects. In this report, we provide suggestions on strategies to minimize hyponatraemia in this context.