Nephrotic Range Proteinuria Research Articles

Prevalence and Patterns of Renal Involvement Among Patients With Systemic Lupus Erythematous at a Tertiary Center.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by widespread inflammation and damage to multiple organ systems. One of the most common and severe manifestations of SLE is lupus nephritis (LN). To determine the prevalence of LN among subjects with SLE and to identify the demographic, clinical, and laboratory parameters of SLE in subjects diagnosed with LN. This is a descriptive study conducted at a tertiary hospital. Medical records were reviewed from outpatients who visited between January 2015 and October 2019 and who has fulfilled the classification criteria for diagnosis of SLE and had LN. Among 365 patients with SLE, 36% had LN. The most prevalent World Health Organization class of LN was IV, which significantly correlated with both abnormal creatinine levels and nephrotic range proteinuria. Elevated serum creatinine correlated with the presence of hypertension and thrombocytopenia. Cutaneous manifestations were noted to be present in 100% of LN patients, followed by arthritis and/or arthralgia (82.9%), anemia (94.6%), and lymphopenia (87.6%). This study aids in the recognition of the demographic, clinical, laboratory features, and the histological patterns of LN patients in Saudi Arabia, that probably has a role in the development and disease progression. A significant correlation was found between abnormal kidney function and hypertension, thrombocytopenia and nephrotic range proteinuria. The presence of World Health Organization class IV LN correlated with both impaired kidney function and nephrotic range proteinuria.

S3211 Weight Loss, Ascites, and Diarrhea as the Presenting Symptoms for Pseudo-Pseudo Meigs Syndrome

Introduction: Pseudo-pseudo Meigs syndrome (PPMS) is a rare presentation of systemic lupus erythematous (SLE) characterized by ascites, pleural effusion, and elevated CA-125 level. Case Description/Methods: A 30-year-old woman with SLE and history of small bowel obstruction presented with diarrhea, weight loss, anasarca, and alopecia. She was initially tachycardic and hypertensive. Her exam revealed profound anasarca with ascites and bilateral pleural effusions. Labs were notable for Cr=5.65 mg/dL (baseline 0.7 mg/dL), spot protein/creatinine=3.9, ferritin=554.6 ng/ml, ESR=145 mm/Hr, CRP=6 mm/Hr, C3=49 mg/dL, C4=19 mg/dL, unremarkable FSH and LH, +ANA, dsDNA 356 U/ml, and +pANCA/MPO. Outpatient workup showed elevated CA-125 to 260.8 U/mL but ovarian malignancy was ruled out by MRI and CT abdomen/pelvis. Transvaginal ultrasound was normal. Inflammatory bowel disease was ruled out by EGD and colonoscopy during a previous hospitalization. Renal ultrasound showed bilateral hydronephrosis. The patient underwent a paracentesis (SAAG 1.3), and thoracentesis that showed total serum protein 4.2 g/dl, pleural fluid LDH 67 U/L, no serum LDH or pleural protein available. Kidney biopsy demonstrated class IV / V lupus nephritis. She was treated with a three-day course of pulse dose methylprednisolone followed by prednisone, hydroxychloroquine, and furosemide infusion. Her symptoms mostly resolved and CA-125 trended down to 27 U/mL. Discussion: PPMS is a rare condition with few cases reported in the literature. This case illustrates the challenges of evaluating abdominal symptoms and ascites in patients with SLE, and the importance of a kidney biopsy in the evaluation of nephrotic range proteinuria. Due to infrequency and concern for malignancy due to elevated CA-125 level, patients with this syndrome undergo extensive workup. CA-125 has been shown to be elevated due to inflammatory markers enhancing its expression in peritoneal mesothelial cells. Prior publications have shown the correlation of CA-125 with extent of serositis in PPMS. Additionally, our patient has many other clinical features reported in PPMS patients including elevated ferritin, alopecia, and positive pANCA. CT scan of abdomen and pelvis is essential in the workup of this syndrome to rule out ovarian malignancy. Moreover, imaging may exclude mesenteric vasculitis, an uncommon feature of SLE which can be seen as targetoid lesions of the bowel on CT scan. Steroids are the treatment for PPMS.

OA19 A case of severe refractory lupus enteritis and nephritis that remitted with Obinutuzumab

Introduction/BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease that can affect almost any organ system but gastrointestinal (GI) involvement is very rare. Obinutuzumab is a humanised type II anti-CD20 monoclonal antibody that is licensed to treat haematological malignancies. It has been used in a small number of SLE patients with secondary non-depletion non-response (2NDNR) to Rituximab and appears to be effective in lupus nephritis (LN) as outlined in the NOBILITY trial. We present a case of refractory lupus enteritis (LEn) and LN in a patient with 2NDNR to repeated Rituximab cycles that achieved remission with Obinutuzumab.Description/MethodA 19-year-old African woman was diagnosed with SLE in 2018 after presenting with polyarthritis without systemic involvement. Blood tests showed leucopenia, positive antinuclear antibody, anti-double-stranded DNA >200 IU/ml and hypocomplementaemia. Prednisolone and Methotrexate were commenced. However, one month later she presented to hospital with generalised abdominal pain, vomiting and diarrhoea. CT abdomen demonstrated significant small bowel wall thickening with mucosal hyperenhancement. Multidisciplinary team (MDT) input confirmed likely LEn. She was treated successfully with intravenous Methylprednisolone and Rituximab. Total parenteral nutrition was required for two weeks.Unfortunately, four further hospital admissions followed over the next six months due to GI symptoms, transient acute kidney injury and moderate proteinuria. Small bowel oedema persisted on MRI, three months after the CT. Renal biopsy demonstrated class 2 LN. Intravenous methylprednisolone helped and further Rituximab was given but she had infusion reactions. Six months later she re-presented with abdominal pain, synovitis and had nephrotic range proteinuria. She was treated again for LEn after gastroenterology input. Further Rituximab was given (MabThera instead of Truxima) but reactions still occurred and her B cells were non-deplete. Repeat renal biopsy confirmed class 4 LN and intravenous Cyclophosphamide (Euro-Lupus regimen) was commenced. This was repeated seven months later due to persisting high disease activity and proteinuria despite a short trial of intravenous Belimumab. However, she was admitted to hospital with colitis on CT after completing the second course of Cyclophosphamide. MDT decision was to treat with Obinutuzumab. Since commencing treatment eighteen months ago, her SLE has dramatically improved and she feels well for the first time. SLEDAI-2K score is 2 (16 pre-treatment), renal function has recovered with mild proteinuria. Anti-double-stranded DNA has reduced from >200 to 52.9 IU/ml and complements normalised. She remains on Prednisolone 5mg daily and Tacrolimus and a third maintenance dose of Obinutuzumab is planned.Discussion/ResultsLEn has been reported in only 0.2-5.8% of SLE cases. It is defined by the British Isles Lupus Assessment Group (BILAG 2004) by either vasculitis or inflammation of the small bowel supported by imaging or histology. Its pathogenesis is poorly understood but thought to be related to immune complex deposition and complement activation resulting in intestinal capillary leak and submucosal oedema. Symptoms are non-specific and a review by Janssens et al. (2013) suggested abdominal pain (97%), ascites (78%), nausea (49%), vomiting (42%) and diarrhoea (32%) were the most common symptoms in patients with LEn. They reported the ileum and jejunum were most commonly affected in LE (84% and 83% respectively), followed by colon (19%), duodenum (17%) and rectum (4%).Abdominal CT is considered to be the first line investigation and ‘classic’ radiological findings are bowel wall oedema (“target sign”), engorgement/increased number of mesenteric vessels (“comb sign”) and increased attenuation of the mesenteric fat (Ha et al. 2000, and Kim et al. 2006). These were all demonstrated on our patient’s initial CT abdomen which showed engorgement of the mesenteric vessels from the proximal jejunum to the proximal ileum.LEn seldom occurs in isolation and usually presents in the context of high disease activity and other systemic involvement. It is often responsive to glucocorticoids and bowel rest but further immunosuppression with Cyclophosphamide or Rituximab might be warranted in refractory cases as in our patient’s case.Obinutuzumab has been shown to be safe, effective and steroid-sparing in renal and non-renal SLE patients with 2NDNR to Rituximab from a case series of 9 patients by Arnold et al. (2022). This applied to LN in our patient and we believe this to be the first case where refractory LEn was treated successfully with Obinutuzumab.Key learning points/ConclusionAlthough very rare, have a high index of suspicion of LEn in SLE patients who present with GI symptoms and typical radiological findings.LEn often occurs with other systemic manifestations including LN and it is important to assess for these at the time of diagnosis of LEn.Obinutuzumab is an emerging treatment for severe SLE particularly 2NDNR to Rituximab and can improve both LN and LEn. We eagerly await results from the current REGENCY and ALLEGORY clinical trials which are assessing Obinutuzumab in renal and non-renal SLE patients respectively.

P38 The gut that leaks

Introduction/BackgroundSystemic lupus erythematosus is a chronic inflammatory autoimmune disease which can affect multiple organ systems. Symptoms of intestinal involvement in SLE may vary from common and non-specific such as heartburn, oral ulcers and dysphagia to less common but more serious including abdominal pain due to serositis and intestinal vasculitis.Description/MethodA 20 year old girl was referred to the gastroenterology team for the management of ascites. Her past medical history included SLE diagnosed aged 10, class IV lupus nephritis, autoimmune haemolytic anaemia secondary to SLE, Haemoglobin H, gastrostomy feeding due to poor growth.At the time of the transition from paediatric to adult service her SLE was under good control. She was on Prednisolone 6 mg on alternate days, Mycophenolate (MMF) 750 mg BD, Septrin 240 mg OD and Enalapril 2.5 mg OD. After the transition, MMF was reduced to 500 mg OD. The rest were unchanged. Serum total protein was 57 (60-80), serum albumin 32 (35-50). Weight was 41.2 kg.Ten months after the transition, she presented with bilateral leg swelling and subsequently tense ascites over 3 weeks. Serum total protein reduced to 31, albumin 13.24 hour urine total protein was 0.15 (0-0.1), urine volume 1.7 L. Serum creatinine 20 µmol/L and eGFR >90. Urine PCR was 16 mg/mmol.Total protein in ascites drain fluid was <20 g/L, albumin <10 g/L, glucose 5.7 mol/L. There were no malignant cells and no growth on enrichment culture.She was referred to the dietitians who advised that her oral intake was adequate.There was no evidence of heart failure on echocardiogram.Small bowel meal showed oedematous bowel wall but no abnormalities in terminal ileum. Coeliac serology was negative.CT abdomen and pelvis showed normal appearances to the liver, hepatic and portal veins; no features of Budd-Chiari syndrome; normal size kidneys; incidental finding of non-occlusive right internal jugular thrombus and moderate lymphadenopathy in mesenteric and retroperitoneal regions.She developed swelling in the right calf. Doppler ultrasound confirmed major DVT with occlusive thrombus extending to distal superficial femoral veins. Clots in inferior vena cava and portal veins were excluded.Discussion/ResultsDuodenal biopsy confirmed villous oedema and dilated lymphatics consistent with changes seen in protein losing enteropathy. She was referred to Rheumatology. Prednisolone was increased to 15 mg. The response was rapid with reduction in ascites. MMF was increased to maximum tolerable dose 750 mg AM and 500 mg PM.Hb had been persistently low around 50 during this illness. She had longstanding hypocomplementaemia. C3 dropped to 0.37 (baseline 0.6). C4 remained low around 0.04. IgG was 5.9 (baseline >7). Serology showed DsDNA was 5 (normal range 0-15), positive ANA, trace positive RNP and negative Rheumatoid factor and APL antibodies. CRP was 10.Abdominal lymphadenopathy was felt to be due reactive changes due to active lupus.With increased steroids and immunosuppressants, she improved significantly both clinically and biochemically within a few weeks. Hb rose to over 90, serum albumin > 25 and serum protein above 50 by the end of 3 months after treatment escalation.Warfarin was stopped upon completion of 6 month anticoagulation.On repeat CT, previous abdominal lymphadenopathy had resolved completely. Splenomegaly measuring 17.6 cm was noted. This was discussed in haematology MDT and thought to be due to the haemoglobinopathy and haemolysis.Haemolysis continued to be a challenge. She remained on relatively high dose steroids varying between 20 mg and 10 mg over the years. Vitamin D was prescribed. Weight was very low but stable just above 38 kg.Protein Losing Enteropathy (PLE) is rare but recognised in SLE. It typically occurs in young women with clinically severe disease with multi organ involvement. Clinical presentation is characterised by the onset of profound oedema, hypoalbuminaemia in the absence of nephrotic range proteinuria. Severe diarrhoea is present in 50% of the patients. It is important to investigate and exclude other causes of hypoalbuminaemia (e.g cardiac failure, liver diseases, malnutrition) and PLE.Key learning points/ConclusionPLE can be the initial manifestation of SLE.Lupus nephritis and PLE can be present successively or simultaneously in a lupus patient.Stringent diagnostic evaluation is required to exclude other mimicking conditions.Multidisciplinary team involvement is crucial in the management of patients with multi-organ involvement.PLE associated with SLE usually responds well to corticosteroids. However additional immunosuppressant(s) are generally required to treat other SLE symptoms as well as to help with the steroid reduction regime.As well as treating the underlying disease, advice from dietitians is important to improve and maximise the nutritional status of these patients.A clinically significant hyper-coagulable state is reportedly attributed to PLE associated with SLE. Therefore, VTE prophylaxis especially in hospitalised patients is recommended. Moreover, clinicians should have high index of suspicion for VTE in these patients with multiple risk factors to arrange early appropriate investigations and treatment plan.

Lithium-induced nephropathy; One medication with multiple side effects: a case report

BackgroundLithium carbonate is commonly used in the treatment of bipolar disorder. A spectrum of side effects is associated with lithium, including nephrogenic diabetes insipidus, renal tubular acidosis, chronic tubulointerstitial nephropathy, and minimal change disease. Although the former three adverse effects are well-known, minimal change disease is relatively rare.Case presentationWe herein report a case of lithium therapy-induced minimal change disease with concurrent chronic tubulointerstitial nephropathy. A 66-year old man with bipolar disorder treated by lithium for 20 years, presented to the hospital with anasarca and decreased urine output for 4 weeks. The medical history also included hyperlipidemia, hypertension, and benign prostatic hyperplasia. Further laboratory investigation revealed elevated serum lithium (2.17 mmol/L), potassium (6.0 mmol/L), and creatinine levels (2.92 mg/dL), nephrotic range proteinuria, and hypoalbuminemia. Lithium was discontinued and the patient was treated with intravenous fluids. He underwent a kidney biopsy, which showed findings consistent with minimal change disease with concurrent acute tubular injury and chronic tubulointerstitial nephropathy. The patient was subsequently treated with steroids in an outpatient setting. He did not respond to the treatment, and hemodialysis was started.ConclusionBased on the previously reported cases and review of literature, occurrence of lithium-associated minimal change nephropathy is rare. Patients with lithium-associated minimal change disease and acute tubular injury usually respond to discontinuation of lithium therapy and/or steroid treatment. In this case, minimal change nephropathy was steroid-resistant and kidney function of the patient reported here did not recover after 6-month follow-up. We postulated the underlying cause to be minimal change disease with chronic tubulointerstitial nephropathy due to long-term lithium use. This case provides an example of a rare side effect of lithium-induced minimal change nephropathy with chronic tubulointerstitial nephropathy in addition to its well-known complication of interstitial nephritis or diabetes insipidus. In our opinion, these patients likely have much worse clinical outcome.

Traditional indigenous medicines are an etiologic consideration for NELL1-positive membranous nephropathy

Traditional indigenous medicines are an etiologic consideration for NELL1-positive membranous nephropathy

The association between hypothyroidism and proteinuria in patients with chronic kidney disease: a cross-sectional study

Hypothyroidism is known to be correlated with kidney function and nephrotic range proteinuria. However, it is uncertain whether non-nephrotic proteinuria is associated with hypothyroidism. This study aimed to evaluate the association of proteinuria and hypothyroidism in chronic kidney disease (CKD) patients. We conducted a cross-sectional study composed of 421 CKD patients in a single hospital with measurements of 24-h urine protein excretion (UP) and thyroid function tests. Spearman correlation analysis revealed that 24-h Cr clearance (24hrCcr) was positively (r = 0.273, p < 0.001) and UP was negatively (r = − 0.207, p < 0.001) correlated with free triiodothyronine. Frequency distribution analysis stratified by CKD stage and UP for hypothyroidism revealed that the prevalence of hypothyroidism was higher among participants with higher CKD stage and nephrotic range proteinuria. Multivariate logistic regression analysis revealed that 24hrCcr and UP were significantly correlated with hypothyroidism (24hrCcr/10 mL/min decrease: odds ratio [OR], 1.29; 95% confidence interval [CI], 1.18–1.41; UP/1 g increase: OR, 1.10; 95% CI, 1.03–1.17). In addition, nephrotic range proteinuria, but not moderate UP (UP: 1.5–3.49 g/day), was significantly correlated with hypothyroidism compared to UP < 0.5 g/day. In summary, decreased kidney function and nephrotic range proteinuria, not non-nephrotic proteinuria, are independently associated with the hypothyroidism.

The diagnostic value of native kidney biopsy in low grade, subnephrotic, and nephrotic range proteinuria: A retrospective cohort study.

In nephrotic range proteinuria of adult-onset, kidney biopsy is the diagnostic gold standard in determining the underlying cause of disease. However, in low grade or subnephrotic proteinuria the diagnostic value of kidney biopsy as first-line diagnostics is less well established. We conducted a retrospective analysis of all native kidney biopsies at our institution (n = 639) between 01/2012 and 05/2021 for comparison of histological diagnoses and clinical outcomes stratified by amount of proteinuria at the time of kidney biopsy: A: <300mg/g creatinine (low grade), B: 300-3500mg/g creatinine (subnephrotic), C >3500mg/g creatinine (nephrotic). Nephrotic range proteinuria was associated with the highest frequency (49.3%) of primary glomerulopathies followed by subnephrotic (34.4%) and low grade proteinuria (37.7%). However, within the subnephrotic group, the amount of proteinuria at kidney biopsy was linearly associated with renal and overall survival (HR 1.05 per Δ100mg protein/g creatinine (95% CI: 1.02-1.09, p = 0.001)) independent of present histological diagnoses and erythrocyturia. Frequency of primary glomerulopathies supports to perform kidney biopsy in patients with subnephrotic proteinuria. These patients have a substantial risk of ESKD and death upon follow-up. Therefore, diagnostic accuracy including histopathology is essential to guide personalized treatment and avert detrimental courses.

An Unusual Etiology of Proteinuria and Hematuria in a Case with IgA Vasculitis Nephropathy: Nutcracker Syndrome

IgA vasculitis is the most frequent type of vasculitis in children and progresses with the involvement of skin, gastrointestinal system, joints and glomerulonephritis. The most frequent findings of IgAV nephritis are microscopic hematuria and proteinuria ranging from trace amounts to nephrotic levels. The nutcracker syndrome (NCS) is a phenomenon that refers to compression of the left renal vein between the abdominal aorta and superior mesenteric artery. The presenting manifestations are hematuria, orthostatic proteinuria, abdominal pain or left flank pain. Herein we reported a case diagnosed with NCS with regard to persistent microscopic hematuria, intermittent macroscopic hematuria and a fluctuating proteinuria in non-nephrotic levels during the follow up of IgA vasculitis nephritis. A 4,5 year-old boy with rashes extending from the dorsal foot to the sacral regions, arthritis of the ankles and abdominal pain had been admitted to hospital and diagnosed with IgA vasculitis. The total urine analysis revealed +3 proteinuria, and +2 erythrocyte. Nephrotic range of proteinuria was detected in 24-hour urine analysis. The renal biopsy was in accordance with grade II IgA vasculitis nephritis according to the ISKDC classification. The patient was started on an ACE inhibitor and fish oil. In further follow-up, intermittent microscopic hematuria and non-nephrotic range of proteinuria reappeared. The amount of proteinuria was measured in the urine collected during the daytime and the nighttime urine and it was observed that the proteinuria was orthostatic. The patient was re-evaluated regarding etiologies for proteinuria and hematuria. Renal Doppler ultrasonography revealed that the angle between the abdominal aorta and SMA was 14 degrees. Abdominal computed tomography angiography demonstrated that the left renal vein was trapped between aorta and SMA, so the case was diagnosed with NCS. In conclusion, non-glomerular etiologies should be kept in mind in the differential diagnosis of patients with hematuria and/or proteinuria although they are being followed for glomerular pathologies.

P8.053: Case Report: Nephrotic-Range Proteinuria in a Deceased Donor Recipient With Acute Antibody Mediated Rejection And Familiar FSGS

P8.053: Case Report: Nephrotic-Range Proteinuria in a Deceased Donor Recipient With Acute Antibody Mediated Rejection And Familiar FSGS

Comparison between outcomes of IgA nephropathy with nephrotic-range proteinuria and nephrotic syndrome: do podocytes play a role?

Background Nephrotic syndrome (NS) and nephrotic-range proteinuria (NRP) are uncommon in IgA nephropathy (IgAN), and their clinicopathology and prognosis have not been discussed. Podocytes may play an important role in both clinical phenotypes. Methods We investigated 119 biopsy-proven IgAN patients with proteinuria over 2 g/d. The patients were divided into three groups according to proteinuria level: the overt proteinuria (OP) group, NS group, and NRP group. In addition, according to the severity of foot process effacement (FPE), the patients were divided into three groups: the segmental FPE (SFPE) group, moderate FPE (MFPE) group, and diffuse FPE (DFPE) group. The outcome was survival from a combined event defined by a doubling of the baseline serum creatinine and a 50% reduction in eGFR or ESRD. Results Compared with the NRP group, patients in the NS group had more severe microscopic hematuria, presented with more severe endocapillary hypercellularity and had a higher percentage of DFPE. The Kaplan–Meier curve showed that MFPE patients had a better outcome in the NRP group <50% of tubular atrophy/interstitial fibrosis. In the multivariate model, the NRP group (HR = 17.098, 95% CI = 3.835–76.224) was associated with an increased risk of the combined event, while MFPE (HR = 0.260, 95% CI = 0.078–0.864; p = 0.028) was associated with a reduced risk of the combined event. After the addition of renin-angiotensin system inhibitors (RASi), the incidence of the combined event in the MFPE group (HR = 0.179, 95% CI = 0.047–0.689; p = 0.012) was further reduced. Conclusions NS presented more active lesions and more severe FPE in IgAN. NRP was an independent risk factor for progression to the renal endpoint, while MFPE indicated a better prognosis in NRP without obvious chronic renal lesions, which may benefit from RASi.

SGLT-2 inhibitors in nephrotic-range proteinuria: emerging clinical evidence.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a class of novel oral anti-hyperglycemic agents which are increasingly used in clinical practice. SGLT-2 inhibitors improve glycemic control and cardiorenal outcomes, promote weight loss, and reduce blood pressure. Randomized controlled trials have demonstrated that SGLT-2 inhibitors reduce proteinuria and delay progression of kidney disease in patients with albuminuria. However, whether SGLT-2 inhibitors have similar benefits in patients with nephrotic-range proteinuria has not been well established. Evidence to date has been limited to case reports, case series and secondary analyses of randomized controlled trials. This is the first comprehensive review on the effectiveness of SGLT-2 inhibitors for the treatment of patients with nephrotic-range albuminuria or proteinuria. Overall findings support a likely beneficial role of SGLT-2 inhibitors in reducing proteinuria and delaying chronic kidney disease progression in patients with nephrotic-range proteinuria.

The appearance of C1q deposition in transplanted kidney allografts and its clinical and histopathologic features.

BackgroundC1q nephropathy is an uncommon type of glomerulonephritis characterized by extensive and dominant C1q mesangial deposition in the absence of systemic lupus erythematosus. However, there are limited studies about C1q deposition in renal allografts. This study aimed to report the prevalence of C1q deposition in transplanted kidney allograft biopsies and describe its clinical and histopathologic features.MethodsBetween January 2005 and December 2018, a total of 1,742 kidney transplantations were performed at Seoul National University Hospital. All renal allograft biopsies (n=10,217) of these patients were retrospectively screened for C1q deposition. C1q deposition was detected in the renal allograft biopsies of 104 patients (6.0%). Only 28 cases (1.6%) had intense (≥2+) C1q dominance and were reviewed in this study.ResultsAmong the 28 cases, only four (14.3%) had accompanying proliferative glomerulonephritis. Most did not have any other glomerular changes on light microscopy. No patients had nephrotic-range proteinuria at the time of biopsy. A follow-up biopsy was undertaken in 15 of the cases (53.6%). In these follow-up biopsies, C1q deposition either completely disappeared (n=13, 86.7%) or showed diminished staining (n=2, 13.3%).ConclusionsThe prevalence of dominant or codominant C1q deposition in transplanted renal allograft biopsies was 1.6%. Most cases did not have any other accompanying glomerular changes. The follow-up biopsies of these allografts showed spontaneous disappearance or diminished staining of C1q deposition. These findings suggest that C1q deposition found in renal allografts is most likely clinically benign, although this possibility should be confirmed in further large-scale studies.

Mycophenolate Mofetil for Severe IgA Vasculitis Nephropathy in Children: An Observational Study

Rationale & ObjectiveIndividuals with IgA vasculitis nephritis (IGAVN) may develop rapidly progressive glomerulonephritis and/or nephrotic-range proteinuria, which are associated with worse prognosis. We report our experience of treatment of children with IGAVN with nephrotic-range proteinuria.Study DesignCase series.Setting & ParticipantsWe retrospectively analyzed all children who presented with IGAVN, cutaneous purpura, and nephrotic-range proteinuria from January 1, 2000 until December 31, 2018.OutcomeWe evaluated time required to achieve remission of proteinuria, resolution of hematuria, and glomerular filtration rate (GFR) at 12 months and last follow-up.ResultsTwelve patients, 8 boys and 4 girls, mean age 7.5 years (range 4-15) were included in the study. Mean urinary protein to creatinine ratio (UPC) was 12.5 ± 8.7 mg/mg and GFR 90.7 ± 19.1 mL/min/1.73 m2 before initiation of immunosuppression. All patients were treated with steroids and mycophenolate mofetil. Mean UPC declined progressively from 12.5 mg/mg to 4.6, 2.7, 0.3, and 0.2 mg/mg after 1, 3, 6, and 12 months, respectively. All patients achieved remission of proteinuria (UPC <0.3 mg/mg) and normalization of kidney function (GFR 102.2 ± 8.0 mL/min/1.73 m2) at 12 months. Immunosuppression was successfully withdrawn in all patients, and at last follow-up (mean 33.5 months), all patients except one remained in remission. All patients except one that relapsed maintained normal GFR at the last follow-up.LimitationsRetrospective study, single-center experience, no standard immunosuppressive protocol, lack of control group.ConclusionsRemission can be achieved in patients with IGAVN and nephrotic-range proteinuria using mycophenolate mofetil-based immunosuppression. Magnitude of proteinuria is a key laboratory finding that correlates with time to achieve remission. Prolonged follow-up of patients with severe IGAVN is warranted.

Quantifying the benefits of remission duration in focal and segmental glomerulosclerosis.

Although the clinical benefit of obtaining a remission in proteinuria in nephrotic patients with focal segmental glomerulosclerosis (FSGS) is recognized, the long-term value of maintaining it and the impact of relapses on outcome are not well described. We examined the impact of remissions and relapses on either a 50% decline in kidney function or end-stage kidney disease (combined event) using time-dependent and landmark analyses in a retrospective study of all patients from the Toronto Glomerulonephritis Registry with biopsy-proven FSGS, established nephrotic-range proteinuria and at least one remission. In the 203 FSGS individuals with a remission, 89 never relapsed and 114 experienced at least one relapse. The first recurrence was often followed by a repeating pattern of remission and relapse. The 10-year survival from a combined event was 15% higher in those with no relapse versus those with any relapse. This smaller than anticipated difference was related to the favourable outcome in individuals whose relapses quickly remitted. Relapsers who ultimately ended in remission (n=46) versus in relapse (n=68) experienced a 91% and 32% 7-year event survival (P<.001), respectively. Using time-varying survival analyses that considered all periods of remission and relapse in every patient and adjusting for each period's initial estimated glomerular filtration rate, the state of relapse was associated with a 2.17 (95% confidence interval 1.32-3.58; P=.002) greater risk of experiencing a combined event even in this FSGS remission cohort. In FSGS, unless remissions are maintained and relapses avoided, long-term renal survival remains poor. Treatment strategies addressing remission duration remain poorly defined and should be an essential question in future trials.

Renal Transplantation in Pure Autonomic Failure.

Renal Transplantation in Pure Autonomic Failure.

Multicentric Carpotarsal Osteolysis Syndrome Associated Nephropathy: Novel Variants of MAFB Gene and Literature Review.

Multicentric carpo-tarsal osteolysis (MCTO) is a rare osteolysis syndrome mainly involving carpal and tarsal bones usually presenting in early childhood. MCTO has autosomal dominant inheritance with heterozygous mutation in the MAFB gene. The skeletal disorder is often associated with chronic kidney disease. Data on clinical characterization and best treatment option of MCTO-associated nephropathy are scarce and mostly limited to case reports. With the aim to better define the phenotype and long-term outcomes of MCTO-associated nephropathy, we launched an online survey through the Workgroup for hereditary glomerulopathies of the European Rare Kidney Disease Network (ERKNet). Overall, we collected clinical and genetic data of 54 MCTO patients, of which 42 previously described and 12 new patients. We observed a high rate of kidney involvement (70%), early age of kidney disease onset, nephrotic-range proteinuria, and a kidney survival around of 40% at long-term follow-up. Our finding confirmed the heterogeneity of clinical manifestations and widen the spectrum of phenotypes resulting from MCTO-associated nephropathy. Furthermore, we report the first case of complete remission after treatment with cyclosporine A. We demonstrated that multidisciplinary care is essential for MCTO patients and early referral to nephrologists is therefore warranted to facilitate prompt treatment.

A case of Gitelman syndrome with membranous nephropathy

BackgroundGitelman syndrome (GS) is a rare autosomal recessive inherited salt-losing tubulopathy (SLT). Here, we report, for the first time, a case of GS overlapping nephrotic syndrome (NS) related to PLA2R-associated membranous nephropathy (MN).Case presentationWe described a male patient had a 4-year history of recurrent fatigue. Serum biochemistry revealed hypokalemia with renal potassium wasting, hypomagnesemia, metabolic alkalosis, hyperreninemia, hypocalciuria, as well as nephrotic-range proteinuria, hypoalbuminemia, and elevated serum anti-phospholipase A2 receptor (PLA2R) antibody. Gene sequencing identified compound heterozygous mutations in SLC12A3 [c.536T > A(p.V179D) and c.1456G > A(p.D486N)]. The unusual association of SLTs and nephrotic-range glomerular proteinuria prompted us to perform a renal biopsy. Renal biopsy showed idiopathic MN. Due to the potential to activate the sodium-chloride co-transporter (NCC) and cause hyperkalemia, tacrolimus was selected to treat NS. Following treatment with potassium chloride, magnesium oxide, low-dose glucocorticoid combined with tacrolimus, the fatigue significantly improved, and concurrently hypokalemia, hypomagnesemia were corrected and NS was remitted.ConclusionsRenal biopsy should be warranted for GS patients with moderate to nephrotic-range proteinuria. Tacrolimus was preferred to the management of GS patients with NS.

Síndrome nefrótico secundario a preeclampsia: presentación, manejo y evolución clínica observados en 5 años de experiencia

IntroductionNephrotic syndrome (NS) is rare during pregnancy. The main cause is severe pre-eclampsia (PR). Our aim was to describe the clinical presentation, analytical features, medical management, and progress of women with NS due to PE. Materials and methodsA descriptive, retrospective study, conducted from 01/01/2017 to 01/01/2022 (5years). Women with a gestational age (GA) ≥20weeks were included in the study, hospitalised due to hypertensive disorders in pregnancy (HDP), with no evidence of kidney damage prior to gestation. ResultsOf the 652 HDP, 452 PE and 21 NS were identified. Maternal age was 25±5.7 years, GA at diagnosis was 33.1±5.1 weeks. All the women had facial and peripheral oedema: 5 pleural effusion, 3 pericardial effusion, and 2 anasarca. Their p24 was 6.17±2.34grams (3.10-10.8), serum albumin 2.5±0.27g/dL (2.10-2.90), and serum cholesterol 281.4±21.7mg/dL (251-316). Thirteen developed maternal complications: acute kidney damage, pulmonary oedema, dilated cardiomyopathy, eclampsia, and HELLP syndrome. They all remained hypertensive postpartum, and required a combination of two to three antihypertensive drugs. They all received statins postpartum, and angiotensin converting enzyme (ACE) inhibitors to manage proteinuria. None developed hyperkalaemia or creatinine elevation. Hospital stay was 10.4±3.7days. All nephrotic range proteinuria parameters reversed prior to discharge. No deaths were recorded. ConclusionPresentation ranged from peripheral oedema to serous involvement. Severity of proteinuria varied. Use of ACE inhibitors did not precipitate hyperkalaemia or kidney failure. Maternal complications were frequent, but no deaths were recorded.

Induction therapy and outcome of proliferative lupus nephritis in the top end of Northern Australia – a single centre study retrospective study

BackgroundLupus nephritis is a common manifestation of Systemic Lupus Erythematosus. Mycophenolate is recommended by guidelines for induction therapy in patients with proliferative lupus nephritis and nephrotic range proteinuria Class V lupus nephritis. Indigenous Australians suffer disproportionally from systemic lupus erythematosus compared to non-Indigenous Australians (Anstey et al., Aust N Z J Med 23:646–651, 1993; Segasothy et al., Lupus 10:439–444, 2001; Bossingham, Lupus 12:327–331, 2003; Grennan et al., Aust N Z J Med 25:182–183, 1995).MethodsWe retrospectively identified patients with newly diagnosed biopsy-proven class III lupus nephritis, class IV lupus nephritis and class V lupus nephritis with nephrotic range proteinuria from 1st Jan 2010 to 31st Dec 2019 in our institution and examined for the patterns of prescribed induction therapy and clinical outcome. The primary efficacy outcome of interest was the incidence of complete response (CR) and partial response (PR) at one-year post diagnosis as defined by the Kidney Disease: Improving Global Outcome (KDIGO) guideline. Secondary efficacy outcome was a composite of renal adverse outcome in the follow-up period. Adverse effect outcome of interest was any hospitalisations secondary to infections in the follow-up period. Continuous variables were compared using Student’s t-test or Mann–Whitney U-test. Categorical variables were summarised using frequencies and percentages and assessed by Fisher’s exact test. Time-to-event data was compared using the Kaplan–Meier method and Log-rank test. Count data were assessed using the Poisson’s regression method and expressed as incident rate ratio.ResultsTwenty of the 23 patients included in the analysis were managed with mycophenolate induction upfront. Indigenous Australian patients (N = 15), compared to non-Indigenous patients (N = 5) received lower cumulative dose of mycophenolate mofetil over the 24 weeks (375 g vs. 256 g, p < 0.05), had a non-significant lower incidence of complete remission at 12 months (60% vs. 40%, p = 0.617), higher incidence of composite renal adverse outcome (0/5 patients vs. 5/15 patients, p = 0.20) and higher incidence of infection related hospitalisations, (incident rate ratio 3.66, 95% confidence interval 0.89–15.09, p = 0.073).ConclusionMycophenolate as upfront induction in Indigenous Australian patients were associated with lower incidence of remission and higher incidence of adverse outcomes. These observations bring the safety and efficacy profile of mycophenolate in Indigenous Australians into question.