Need For Kidney Biopsy Research Articles

AKI after Vancomycin Treatment: Need for Kidney Biopsy

AKI after Vancomycin Treatment: Need for Kidney Biopsy

Anti-Phospholipase A2 Receptor Antibody (Anti-PLA2R) Testing to the Rescue

Serological testing for M-type anti-phospholipase A2 receptor antibodies (antiPLA2R Ab) has abrogated the need for kidney biopsy to diagnose membranous nephropathy in the appropriate clinical setting. We report a case of a 63-year-old hypertensive male who presented with nephrotic syndrome associated with autosomal dominant polycystic kidney disease which was effectively diagnosed with the use of antiPLA2R Ab test. He achieved complete remission upon treatment with Rituximab. Hitherto, all anecdotal case reports of this uncommon association were diagnosed only by kidney biopsy. We highlight the usefulness of PLA2RAb especially in such cases of difficult-to-biopsy kidneys.

Effect of daratumumab on light chain reduction in newly diagnosed multiple myeloma with light chain cast nephropathy.

7554 Background: Light chain cast nephropathy (LCCN) is present in 16-31% of patients (pts) in newly diagnosed multiple myeloma (NDMM). In pts with an involved serum free light chain (iFLC) >150mg/dL and predominant LC proteinuria, the probability of LCCN is high enough for a clinical diagnosis without the need for kidney biopsy. Early mortality is higher in pts with renal impairment (RI) who did not achieve a renal response (RR), and a rapid reduction in iFLC may predict RR. While the use of bortezomib and dexamethasone (Vd) in upfront therapy has led to marked improvements in outcomes, the optimal regimen is unclear. Methods: We included pts with NDMM and RI (creatinine >2 mg/dL or eGFR <40 ml/min/1.73m2) and a diagnosis of LCCN (iFLC >150mg/dL and light chain proteinuria) at a single center from 2005-2023. Pts with >10% albuminuria or a diagnosis of MGRS or amyloidosis were excluded. Primary outcome was FLC response (iFLC <50mg/dL and >90% reduction, FLC-R) at day 30 (d30). Other outcomes included hematologic response (partial response or better) at d30 and RR (minimal response or better) at d90, based on International Myeloma Working Group criteria. Results: We included 51 pts with characteristics depicted in the table. All pts received therapy with Vd, adding cyclophosphamide (VCd) in 26 (51%), daratumumab (dara, DVd) in 13 (25%), both (DVCd) in 6 (12%) and alone in 6 (12%). At d30, 11 pts (58%) in dara-containing regimens (DVd, DVCd) and 10 pts (31%) in non-dara-containing regimens (Vd, VCd) achieved a FLC-R (p=0.08); dara was associated with higher odds of achieving a FLC-R at d30 (OR 2.9, p=0.03) after adjusting for age, stage and eGFR at diagnosis. At d90, pts receiving dara had a higher rate of RR than those who did not (69% vs 58%, p=0.5); dara was associated with higher odds of a RR at d90 (OR 1.6, p=0.5). After adjusting for age, stage and eGFR at diagnosis, achieving a FLC-R at d30 was associated with higher odds of a RR at d90 (OR 8.9, p=0.02). Conclusions: Prompt reduction of iFLC is an important objective during the early treatment of LCCN in order to achieve a RR, and dara increases the odds of achieving a FLC-R. The use of dara led to higher odds of a RR at d90, but not statistically significant. We confirmed that achieving a FLC-R at d30 was associated with achieving a RR at d90. Our results suggest that the role of a dara should be explored in prospective studies for the upfront treatment of LCCN in NDMM. [Table: see text]

A novel likely pathogenic CLCN5 variant in Dent’s disease

BackgroundThe majority of cases of Dent’s disease are caused by pathogenic variants in the CLCN5 gene, which encodes a voltage-gated chloride ion channel (ClC-5), resulting in proximal tubular dysfunction. We present three members of the same family and one unrelated paediatric patient with the same insertion-deletion CLCN5 variant. The identification of these patients and positive familial segregation led to the re-classification of this variant from one of unknown significance to one of likely pathogenicity.Case presentationA 41 year old male presented with end stage kidney failure, proteinuria and haematuria. Whole genome sequencing identified an insertion-deletion variant in CLCN5, resulting in a missense change (c.1744_1745delinsAA p.(Ala582Lys)). His brother and nephew, who both exhibited renal impairment, haematuria, proteinuria, glycosuria and nephrocalcinosis, were found to have the same variant. In addition, genetic testing of an unrelated paediatric patient who presented with proteinuria and hypercalciuria, demonstrated the same variant.ConclusionsThe identification of this novel variant in four individuals with features of Dent’s disease, has led to the re-classification of the variant to one of likely pathogenicity.As a result, our patients and any future patients with the same variant can be offered a likely diagnosis, without the need for kidney biopsy, and their family members can be offered genetic screening.

The need for kidney biopsy in the management of side effects of target and immunotherapy.

The introduction of innovative therapies, resulting from revisiting cancer as a disease of the immune system, has changed the scenario of complications. These new classes of drugs, such as targeted therapies and immune checkpoint inhibitors, assure substantial advantages in cancer therapy, despite some side effects affecting various organs, including the kidney. Histological evaluations of kidney disorders induced by targeted/immunotherapy are limited. In this study we examined the histological features of patients treated with new cancer agents who underwent a kidney biopsy for new onset kidney failure and/or urinary abnormalities. The cohort included 30 adult patients. The most frequently administered therapies were immunotherapy (30%), targeted therapy (26.7%), immunotherapy plus targeted therapy (13.3%), immunotherapy plus chemotherapy (13.3%), targeted therapy plus chemotherapy (16.7%). The most common histological finding was tubular interstitial nephritis (30%) that was associated with acute tubular necrosis in 4 cases, and thrombotic microangiopathy (23.3%). After kidney biopsy, 16 of the 30 patients were treated according to the histological diagnosis. Fourteen patients were treated with steroids. One patient with membranous nephropathy was treated with a single dose of rituximab. A patient with severe thrombotic microangiopathy requiring dialysis received a treatment with eculizumab for 3 months. Overall some renal response was obtained in all patients treated with glucocorticoids, while complete kidney response was achieved in the patient treated with rituximab. Cancer treatment was resumed without change in 21 out of 30 patients. Kidney biopsy is critical for the management of kidney toxicities and should be strongly encouraged for patients showing adverse kidney effects of novel cancer agents.

Characterizing predictors of non-diabetic kidney disease (NDKD) in diabetic patients.

Diabetic kidney disease (DKD) is the chief cause of renal involvement in diabetic patients. It is primarily a clinical diagnosis. Non-diabetic kidney disease (NDKD) may be missed if they are not biopsied. In this study, we describe the spectrum of NDKD and evaluate the predictors considered for planning a biopsy in diabetic patients with kidney disease. In a retrospective cohort study, diabetic patients who underwent kidney biopsy at our centre between May 2006 and July 2019 were evaluated for NDKD. 321 diabetic patients who underwent kidney biopsy were analyzed. Mean age was 49.3 ± 12.4years and 71% were males. 75.8% patients had hypertension and 25.2% had diabetic retinopathy. Based on the kidney biopsy, patients were classified as DKD-127 (39.6%), NDKD-179(55.8%) and combined DKD + NDKD-15(4.7%). Overall, the most commonly diagnosed pathology was membranous nephropathy-MN (17%), followed by IgA nephropathy (16.0%) and focal segmental glomerulosclerosis-FSGS (14.9%). In patients with DKD + NDKD, IgA nephropathy (53.3%) was predominant. 165 (51.4%) patients had a diagnosis potentially amenable to a specific therapy. On multivariate analysis, female gender [OR 2.07 (1.08-3.97), p = 0.02], absence of diabetic retinopathy [OR 7.47 (3.71-15), p < 0.001] absence of hypertension [OR 3.17 (1.56-6.45), p = 0.001] and duration of diabetes ≤ 24months [OR 3.67(1.97-6.84), p < 0.001], were independent predictors for NDKD while the absence of nephrotic range proteinuria [OR 1.73 (0.98-3.05), p 0.05] showed a trend towards significance. Astute use of kidney biopsy can detect potentially treatable NDKD in a large number of diabetic patients with glomerular diseases being the predominant diagnosis. A combination of risk factors needs to be considered to guide the need for kidney biopsy in diabetic patients.

Kidney Dysfunction Post-Allogeneic Transplant: High Incidence of TMA and Kidney GvHD

Introduction:Kidney dysfunction is an important problem in adult recipients of allogeneic stem cell transplantation (HSCT) and independently predicts overall survival and non-relapse mortality. Kidney dysfunction occurs in ~50% of transplant recipients. More than 20% of all survivors of HSCT in long-term follow up develop chronic kidney disease. However, there is currently limited data on the cause and consequences of kidney dysfunction in adult recipients after allogeneic HSCT.Common causes of kidney dysfunction after HSCT include chemotherapy or radiation toxicity, infections, sepsis, hepatic sinusoidal obstruction, drug toxicities due to immunosuppressive medications, thrombotic microangiopathy, as well as acute or graft versus host disease (GvHD). Kidney biopsies are seldom obtained and hence the tissue diagnosis in these patients often remains speculative. Early identification of the causes of kidney dysfunction may help define preventive and therapeutic strategies and improve outcome.Hence, in August 2016, we designed a prospective study at our center to systematically evaluate kidney dysfunction in adult recipients of allogeneic HSCT. Herein we present our initial report of 8 kidney biopsies.Methods:All adult HSCT recipients with kidney dysfunction were evaluated by Nephrologists to determine the need for kidney biopsy. Kidney dysfunction was defined as either (i) acute kidney failure or (ii) proteinuria. Acute kidney failure was defined by the ‘ Kidney Disease: Improving Global Outcomes (KDIGO)‘ criteria. Proteinuria was defined as (i) spot urine albumin to creatinine ratio of ≥1 (equivalent to ≥1 g in 24 hours). Kidney biopsies were done under ultrasound guidance and the tissue specimens were interrogated by light, immunofluorescence and electron microscopy.Results:A total of 8 HSCT recipients (including one patient who had a biopsy prior to Aug 2016) underwent kidney biopsies. The patient and transplant characteristics are summarized in Table 1.Seven of the 8 pts had AML. One patient had NHL in CR2. Four patients received a MUD transplant. Two received MRD transplants. Two received combined haploidentical and single unit cord blood transplant (haplo-cord). Six of the 8 patients received conditioning with fludarabine and melphalan. One patient received additional 400 Gy TBI. One patient received additional azacytidine.Median time to neutrophil engraftment was 13.5 days (range 9-20). Median time to platelet engraftment was 19 days (range 14-76). There were no cases of graft failure. All patients also demonstrated either acute or chronic GvHD of other organs - most commonly skin.All kidney biopsies were performed without complications. Kidney biopsies were done at median 254 days after transplantation (range 126-680). Baseline serum creatinine (mg/dL) prior to transplant was 0.95 (median, range 0.65-1.1, reference range: 0.64-1.27 mg/dL). Creatinine at time of biopsy: 3.0 (median, range 1.53-5.07). Urine albumin/creatinine ratio: 832 (median, range 55-2864, reference range: <30).The kidney biopsy findings are summarized in Table 2. All patients had evidence of endothelial cell injury, either acute or chronic. Three patients had features suggestive of GvHD of the kidney while one patient had BK virus nephropathy.Four of the 8 recipients died; 80 days (median, range 39-124) from the biopsy, 346 days (median, range 178-804) from transplantation. The clinical outcome is summarized in Table 3.Conclusions:Kidney biopsies post-transplant are an important diagnostic tool that should be considered for prolonged kidney dysfunction or proteinuria, particularly in the setting of other post-transplant complications. Our single-center biopsy results highlight the under-recognition of kidney dysfunction complications and complexities observed post-transplant. All kidney biopsies performed were instrumental in treatment planning. Further investigation is needed to define criteria for diagnosis and to understand the pathophysiology. This requires multi-disciplinary engagement as well as a proactive approach for obtaining kidney biopsies. With appropriate transfusion support, percutaneous kidney biopsies were performed safely without complication. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Diagnostic and clinical utility of genetic testing in children with kidney failure.

Genetic kidney disease is well established as an important cause of pediatric kidney failure, and genetic testing might increase diagnostic accuracy, but evidence is limited. This study was conducted to determine the diagnostic yield and clinical impact of genetic testing for children with kidney failure. Patients who were diagnosed with kidney failure before 19 years of age at Children's Hospital of Fudan University from 2009 to 2018 and received next-generation sequencing (NGS) were enrolled. The results for likely pathogenic variants in genes known to cause chronic kidney disease (CKD) were analyzed. A molecular diagnosis was identified in 39.9% (75/188) of children with kidney failure. Specific subtype of clinical category was discerned in 54 (72.0%) patients, kidney disease was reclassified in 7 (9.3%) patients, the unknown etiology of 5 (6.7%) patients was molecularly diagnosed, and the clinical diagnoses of the other 9 (12.0%) patients were confirmed. In addition, genetic diagnosis was considered to have contributed to clinical management, including negating the need for kidney biopsy (26/75, 34.7%), avoiding immunosuppressive therapy (24/75, 32.0%), changing surveillance (48/75, 64.0%), guiding specific treatment (21/75, 28.0%), and guiding peri-transplant management and options for kidney transplantation (12/75, 16.0%). Furthermore, cascade testing was subsequently offered to 34.7% (26/75) of families. Genetic testing identified a molecular diagnosis in nearly 40% of children with kidney failure. Our results confirm that in children with kidney failure, genetic testing can not only establish a specific molecular diagnosis, but has a significant impact on clinical management.

Consensus Guidelines on Management of Steroid-Resistant Nephrotic Syndrome

The management ofsteroid resistant nephrotic syndrome (SRNS) is challenging. These guidelines update existing 2009 Indian Society of Pediatric Nephrology recommendations on its management. Toframe revised guidelines on diagnosis and evaluation, treatment and follow up, and supportive care of patients with the illness. The guidelines combine evidence-based recommendations and expert opinion. Formulation of key questions was followed by systematic review of literature, evaluation of evidence by experts and two face-to-face meetings. Fourteen statements provide updated advice for managing steroid resistance, and underscore the importance of estimating proteinuria and baseline kidney function, and the need for kidney biopsy and genetic screening. Calcineurin inhibitors are recommended as most effective in inducing remission of proteinuria, the chief factor associated with long-term renal survival. Advice on managing allograft recurrence, congenital nephrotic syndrome, and monitoring and supportive care, including transition of care, are described. This revised practice guideline is intended to improve management and patient outcomes, and provide direction for future research.

Consensus guidelines on management of steroid resistant nephrotic syndrome

The management of steroid resistant nephrotic syndrome (SRNS) is challenging. These guidelines update existing 2009 Indian Society of Pediatric Nephrology recommendations on its management.To frame revised guidelines on diagnosis and evaluation, treatment and follow up, and supportive care of patients with the illness.The guidelines combine evidence-based recommendations and expert opinion. Formulation of key questions was followed by systematic review of literature, evaluation of evidence by experts and two face-to-face meetings.Fourteen statements provide updated advice for managing steroid resistance, and underscore the importance of estimating proteinuria and baseline kidney function, and the need for kidney biopsy and genetic screening. Calcineurin inhibitors are recommended as most effective in inducing remission of proteinuria, the chief factor associated with long-term renal survival. Advice on managing allograft recurrence, congenital nephrotic syndrome, and monitoring and supportive care, including transition of care, are described. This revised practice guideline is intended to improve management and patient outcomes, and provide direction for future research.

A multiple methods approach to determine adherence with prescribed mycophenolate in children with kidney transplant.

The aim of this study was, to use a multiple methods approach, including, for the first time, dried blood spot (DBS) sampling with population pharmacokinetic interpretation, to assess adherence to mycophenolate in children with kidney transplant. A second aim was to identify patient/parental factors that influenced adherence and to link adherence behaviour to clinical outcomes. A convenience sample of 33 children with kidney transplant (age≤18years) who had been prescribed mycophenolate for at least 3months were recruited from participating outpatient clinics in the UK and Jordan. Medication adherence was determined via self-report questionnaires, medication refill data from dispensing records, and via mycophenolic acid concentrations in plasma and DBS samples obtained from children during a clinic visit. Through triangulation of results from the different methodological approaches a total of 12 children (36.4%) were deemed to be nonadherent with their prescribed mycophenolate treatment. Logistic regression analysis indicated that nonadherence was significantly associated with the presence of mycophenolate side effects. Poor adherence was positively linked to measures of poor clinical outcomes (hospitalisation and the need for kidney biopsy). Despite the imperative regarding medication adherence to help prevent organ rejection, a significant proportion of children are not fully adherent with their therapy. Side-effects appear to be an important factor leading to nonadherence. Measurement of mycophenolate in DBS samples, coupled with the use of population pharmacokinetics modelling, was a convenient direct approach to assessing adherence in children with kidney transplant and has the potential to be introduced into routine practice.

Supersonic Shear Wave Ultrasonography for Assessing Tissue Stiffness in Native Kidney

Recent years have brought shear wave elastography to the attention of nephrologists as a non-invasive method for detecting kidney fibrosis and, therefore, as a potential tool for reducing the need for kidney biopsy. Few studies are performed on native kidney. We aimed to compare cortical stiffness, assessed by measuring Young's modulus (YM, kPa) with SuperSonic Imaging technology, in patients with various degrees of chronic kidney disease (CKD) compared with healthy individuals. Cortical stiffness was measured by two operators, in different sessions, in 32 patients with CKD stages 3–5 and 20 healthy individuals. Comparison between mean YM values in CKD and those in controls and also between the different stages of CKD was our primary objective. The influence of other possible confounders on YM readings was also investigated and analyzed. Mean YM was significantly greater in CKD patients than in controls. Estimated YM was not able to differentiate the stages of CKD, except stage 5. Intra-subject variability was greater in CKD than in controls. Body mass index was the most important confounder in multiple analyses, in both the CKD and control groups. Our results highlight a positive correlation between increased cortical stiffness and presence of CKD. Further studies are needed to validate this method for implementation in daily clinical practice.

282 - Kidney Dysfunction Post-Allogeneic Transplant: High Incidence of TMA and Kidney GvHD

Abstract Introduction: Kidney dysfunction is an important problem in adult recipients of allogeneic stem cell transplantation (HSCT) and independently predicts overall survival and non-relapse mortality. Kidney dysfunction occurs in ~50% of transplant recipients. More than 20% of all survivors of HSCT in long-term follow up develop chronic kidney disease. However, there is currently limited data on the cause and consequences of kidney dysfunction in adult recipients after allogeneic HSCT. Common causes of kidney dysfunction after HSCT include chemotherapy or radiation toxicity, infections, sepsis, hepatic sinusoidal obstruction, drug toxicities due to immunosuppressive medications, thrombotic microangiopathy, as well as acute or graft versus host disease (GvHD). Kidney biopsies are seldom obtained and hence the tissue diagnosis in these patients often remains speculative. Early identification of the causes of kidney dysfunction may help define preventive and therapeutic strategies and improve outcome. Hence, in August 2016, we designed a prospective study at our center to systematically evaluate kidney dysfunction in adult recipients of allogeneic HSCT. Herein we present our initial report of 8 kidney biopsies. Methods: All adult HSCT recipients with kidney dysfunction were evaluated by Nephrologists to determine the need for kidney biopsy. Kidney dysfunction was defined as either (i) acute kidney failure or (ii) proteinuria. Acute kidney failure was defined by the ‘ Kidney Disease: Improving Global Outcomes (KDIGO)‘ criteria. Proteinuria was defined as (i) spot urine albumin to creatinine ratio of ≥1 (equivalent to ≥1 g in 24 hours). Kidney biopsies were done under ultrasound guidance and the tissue specimens were interrogated by light, immunofluorescence and electron microscopy. Results: A total of 8 HSCT recipients (including one patient who had a biopsy prior to Aug 2016) underwent kidney biopsies. The patient and transplant characteristics are summarized in Table 1. Seven of the 8 pts had AML. One patient had NHL in CR2. Four patients received a MUD transplant. Two received MRD transplants. Two received combined haploidentical and single unit cord blood transplant (haplo-cord). Six of the 8 patients received conditioning with fludarabine and melphalan. One patient received additional 400 Gy TBI. One patient received additional azacytidine. Median time to neutrophil engraftment was 13.5 days (range 9-20). Median time to platelet engraftment was 19 days (range 14-76). There were no cases of graft failure. All patients also demonstrated either acute or chronic GvHD of other organs - most commonly skin. All kidney biopsies were performed without complications. Kidney biopsies were done at median 254 days after transplantation (range 126-680). Baseline serum creatinine (mg/dL) prior to transplant was 0.95 (median, range 0.65-1.1, reference range: 0.64-1.27 mg/dL). Creatinine at time of biopsy: 3.0 (median, range 1.53-5.07). Urine albumin/creatinine ratio: 832 (median, range 55-2864, reference range: The kidney biopsy findings are summarized in Table 2. All patients had evidence of endothelial cell injury, either acute or chronic. Three patients had features suggestive of GvHD of the kidney while one patient had BK virus nephropathy. Four of the 8 recipients died; 80 days (median, range 39-124) from the biopsy, 346 days (median, range 178-804) from transplantation. The clinical outcome is summarized in Table 3. Conclusions: Kidney biopsies post-transplant are an important diagnostic tool that should be considered for prolonged kidney dysfunction or proteinuria, particularly in the setting of other post-transplant complications. Our single-center biopsy results highlight the under-recognition of kidney dysfunction complications and complexities observed post-transplant. All kidney biopsies performed were instrumental in treatment planning. Further investigation is needed to define criteria for diagnosis and to understand the pathophysiology. This requires multi-disciplinary engagement as well as a proactive approach for obtaining kidney biopsies. With appropriate transfusion support, percutaneous kidney biopsies were performed safely without complication. Download : Download high-res image (217KB) Download : Download full-size image Disclosures No relevant conflicts of interest to declare.

Outcome of children with isolated microscopic hematuria without renal biopsy

Introduction: Hematuria (presence of >5 RBCs/HPF) may be a transient outcome or indicator of significant renal disorder in children. Children with neither symptoms of a disease nor a physical abnormality who have microscopic hematuria should be placed in the category of isolated microscopic hematuria (IMH). Objectives: The aim of this study was to evaluate the course of IMH.Patients and Methods: This investigation is an observational study of 124 patients referred to pediatric nephrology clinic from 2002-2012 with IMH. Results: In this study, 124 patients, 40 (32.3%) female and 84 (67.8%) male were evaluated. The mean age was 5.6±2.4 years. The mean follow-up time was 14.3 ± 14.4 months. This mean for 45.2% of the patients, was less than 6 months and for 4% of the patients, it was more than 4 years. The reasons for discovering hematuria were; 66.1% after routine evaluation, 21.8% due to positive family history and 12.1% after urinary tract infection (UTI). In this study, all the laboratory tests and kidney function were normal, except for the presence of microscopic hematuria. Conclusion: It was concluded that IMH without renal failure, hypertension (HTN) and proteinuria is a benign condition with no need for kidney biopsy.

Urinary Procollagen III Aminoterminal Propeptide (PIIINP)

Kidney biopsy (KB), to date the only tool for the evaluation of renal fibrosis, carries specific risks, and its relevance is limited by the small size of renal parenchyma assessed. Thus, a noninvasive alternative to KB is required. Collagen type III amino-terminal propeptide (PIIINP) is a degradation product of collagen type III, the increase of which may reflect an ongoing fibrotic process. In a prospective study including 199 patients with various stages of chronic kidney disease (CKD), the association between urinary PIIINP/creatinine ratio (UPIIINP/Cr), patients' characteristics, and renal fibrosis was assessed. A total of 118 of the patients had UPIIINP/Cr measured simultaneously with the performance of a KB. In patients, median UPIIINP/Cr was 290 ng/mmol versus 93.7 ng/mmol in controls. In univariate analysis, UPIIINP/Cr was correlated with serum creatinine, estimated GFR, CKD stage, presence of coronary artery disease, and nephropathy type (glomerulonephritis versus other types). In multivariate analysis, only estimated GFR and nephropathy type were correlated with UPIIINP/Cr. UPIIINP/Cr was closely correlated with the extent of interstitial fibrosis in KB assessed using two different methods. Moreover, UPIIINP/Cr >800 ng/mmol had a negative predictive value of 94% to detect patients in whom KB will eventually prove "noninformative" (KB leading neither to a definite diagnosis of nephropathy nor to specific treatment). UPIIINP/Cr is a promising fibro-test for the kidney and may alleviate the need for KB in some patients with CKD. Its predictive value for CKD progression deserves evaluation in prospective studies.

In Pilot Study, PET Antibody Identifies Clear-Cell Renal Cancer, Potentially Avoiding Need for Kidney Biopsy

In Pilot Study, PET Antibody Identifies Clear-Cell Renal Cancer, Potentially Avoiding Need for Kidney Biopsy

Kidney biopsy in lupus nephritis: look before you leap

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease primarily affecting women of reproductive age. There is a particular pre-disposition to develop SLE in those of African descent, including a growing incidence in sub-Saharan Africa [1,2]. When compared with white patients, a more aggressive course of disease and poorer outcomes are noted. Such effects are also seen with lupus kidney disease, which is also more common in black patients [3]. Indeed, during the course of their disease, the kidney is a major target organ in up to 60% of patients with SLE, with 25–50% presenting with kidney involvement already at the time of lupus diagnosis. The presentation of lupus nephritis is highly variable, ranging from mild asymptomatic proteinuria to rapidly progressive glomerulonephritis with haematuria and red cell casts. Features invariably include some degree of glomerular proteinuria—nephrotic in 45–65% of the cases. Several studies have illustrated the lack of reliability of diagnoses rendered on the basis of clinical features alone [4,5]. Therefore, making a diagnosis on clinical grounds alone is problematic and risky, underscoring the need for kidney biopsy. With diverse renal histopathological findings possible in SLE-affected patients, biopsy determines not only the diagnosis and prognosis, but also substantially guides management of this complex disease. As the therapeutic armamentarium for lupus nephritis expands, it becomes even more imperative that the correct diagnosis be made prior to instituting therapy. In deciding whether to perform a biopsy, one must balance the risks of the biopsy procedure against the risks of limited diagnostic information, which may result in progression of potentially preventable renal disease or the unnecessary use of a possibly toxic therapy.

Large homozygous deletions of the 2q13 region are a major cause of juvenile nephronophthisis.

Juvenile nephronophthisis (NPH) is a genetically heterogeneous disorder representing the most frequent inherited cause of chronic renal failure in children. We recently assigned a gene (NPH1) to the 2q13 region which is responsible for approximately 85% of cases. Cloning this region in a yeast artificial chromosome contig revealed the presence of low copy repeats. Large-scale rearrangements were detected in 80% of the patients belonging to inbred or multiplex NPH1 families and in 65% of the sporadic cases. Surprisingly, these rearrangements seem to be, in most cases, large homozygous deletions of approximately 250 kb involving an 100 kb inverted duplication. This suggests a common genetic disease-causing mechanism, which could be responsible for the highest frequency of large rearrangements reported in an autosomal recessive trait. Our findings are also of major clinical interest, as they permit the diagnosis in the majority of sporadic cases without the need for kidney biopsy.