Outcomes of minimal change disease without nephrotic range proteinuria.

The aim of this study was to review the morphologic patterns of membranoproliferative glomerulonephritis (MPGN) in 100 Iranian patients using light microscopy (LM) and electron microscopy (EM), and to compare the treatment and outcome in 13 patients with two biopsies. A retrospective study of 713 kidney biopsies of Iranian patients received between 1981 to 1994 was carried out. Of the 713 kidney biopsies, MPGN (n=106) and membranous glomerulopathy (n=112) made up the highest numbers of cases. Among 100 MPGN patients, 55 (55%) were MPGN type I, 10 were type II (10%), and 35 type III (35%). Eighty-three (83%) had nephrotic proteinuria, 39 (39%) had hematuria, and 52 (52%) were hypertensive. Complement levels were estimated in 58, with low C3 in 10. The glomerular involvement was irregular, with focal hypercellularity in 47 patients (47%), widely patent capillaries in 50 (50%), arteriosclerosis in 48 (48%), and with hyaline change in 25 (25%). Follow-up data (22-130 months) was available in 61 (61%) patients: 6 (10%) died after 14-56 months, 27 (44%) were on maintenance hemodialysis for 15-110 months, and three received transplants. Thirteen patients had detailed follow-up and a second biopsy after 24-120 months. All 13 presented with edema and nephrotic range proteinuria, with hematuria and hypertension in five and azotemia in four. Seven of the 13 patients received initial steroids, followed by antiplatelet or antihypertensive drugs. Four (type III) patients received antiplatelet and antihypertension drugs, and two (type III) received only antihypertensive drugs. In the first biopsy, glomerular changes by light microscopy were non-uniform in 7 of 10 (70%) type III MPGN cases. Vascular changes were absent or mild in 11, and moderate in two. In the second biopsies, 10 showed decrease in cellularity, with many open capillaries, persistence of deposits by EM in all, and progression of vascular sclerosis in eight, and tubulointerstitial changes in 10. Among the 13, six were clinically stable, another six received dialysis followed by transplant in three, and one had relapses with episodes of cryoglobulinemia. Three patients died. There is a high incidence of MPGN in Iranian patients, with a substantial number of type III MPGN cases. Second biopsies showed decreased cellularity, but increase in chronic tubulointerstitial and vascular cases. Steroids did not appear to benefit the outcome in types I and III MPGN patients compared to patients who received antihypertensive and antiplatelet treatment without steroids.

BackgroundKidney injury in mixed connective tissue disease (MCTD) is an uncommon manifestation. Prevalence has been reported to be <4% in some cohorts. The frequency of renal involvement in Hispanic patients...

Nephrotic range proteinuria and CD4 count as noninvasive indicators of HIV-associated nephropathy

Aims and objectives: To compare pregnancy outcomes among pre-eclamptic women with nephrotic and non-nephrotic range proteinuria.Methods: This prospective cohort study was conducted from May 2021 to December 2022 at a tertiary care university hospital in South India. We included a total of 278 women diagnosed with preeclampsia, 56 with and 222 without nephrotic range proteinuria in a 1:4 ratio, respectively. The relative risks (RR) of core maternal and perinatal adverse outcomes for preeclampsia among the two groups were compared. Using logistic regression analysis, we calculated the odds ratio adjusted for maternal characteristics (aOR).Results: The women with nephrotic range proteinuria had a higher risk of eclampsia (RR 4.29, 95% CI 2.07-8.89, p<0.01), hemolysis, elevated liver enzymes, low platelet (HELLP) syndrome (RR 6.79, 95% CI 2.8-16.46, p<0.01), abruptio placentae (RR 4.95, 95% CI 2.05-11.97, p<0.01), pulmonary oedema (RR 5.94 95% CI 2.55-13.84, p<0.01), acute kidney injury (RR 4.75 95% CI 1.5-15.02, p 0.003), retinal detachment (RR 23.78 95% CI 2.92-193.5, p <0.01), stillbirth (RR 7.48 95% CI 3.52-15.89, p<0.001), small for gestational age (RR 1.45 95% CI 1.27-1.65, p <0.001), respiratory support (RR 2.06 95% CI 1.12-3.76, p<0.02) and neonatal mortality (RR 3.3 95% CI 1.04-10.43, p 0.04) compared to non-nephrotic range proteinuria. Most of the women with nephrotic proteinuria had early-onset preeclampsia (64.28% versus 36.03%, p<0.01), increasing the risk of prematurity and neonatal morbidity and mortality.Conclusion: In women diagnosed with preeclampsia, the nephrotic range proteinuria was associated with poor maternal and perinatal outcomes and should be considered as a predictor of adverse pregnancy outcomes.

Background: Heavy proteinuria in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) is usually considered to be associated with immune deposits in renal biopsy. Nephrotic ANCA GN without immune deposits (pauci-immune) is rare and has not been studied specially. In this study characteristics of these patients are to be investigated. Methods: Clinical and pathological characteristics from 20 kidney biopsy-proven pauci-immune anti-myeloperoxidase antibody-associated GN patients with nephrotic proteinuria were analyzed and were compared with ANCA GN patients without nephrotic proteinuria. Results: Acute kidney injury (AKI) and gross hematuria were much prevalent but extra-renal involvement was less prevalent in pauci-immune ANCA GN with nephrotic proteinuria than in pauci-immune ANCA GN without nephrotic proteinuria. No more severe hypoalbuminemia, hypercoagulability, hyperlipidemia or higher thrombosis incidence were found between two groups. Compared with patients without nephrotic proteinuria, patients with nephrotic proteinuria had more prevalent crescentic category in histopathology. Proteinuria decreased quickly after treatment but much poorer renal prognosis was found in pauci-immune ANCA GN with nephrotic proteinuria. The results of urinary albumin to total protein ratio and urinary protein electrophoresis showed pauci-immune ANCA GN with nephrotic proteinuria had obvious non-selective proteinuria. Conclusions: Pauci-immune ANCA GN with nephrotic proteinuria do not have more severe hypoalbuminemia, hypercoagulability or hyperlipidemia than patients without nephrotic proteinuria. Non-selective proteinuria might be the reason. However, pauci-immune ANCA GN with nephrotic proteinuria have more prevalent crescentic category in histopathology, higher incidence of AKI, gross hematuria and poorer renal prognosis despite of good sensitivity to therapy of proteinuria.

The association between nonsteroidal anti-inflammatory drugs (NSAIDs) and nephrotic syndrome has long been recognized. Minimal change disease and membranous nephropathy have been the most common findings in those patients in whom a kidney biopsy was performed (1–6). Regarding NSAIDs-related minimal change disease, it is a peculiar type of nephrotic syndrome in which most of reported patients present with a severe AKI accompanying nephrotic syndrome manifestations (edema, proteinuria >3.5 g/d, and hypoalbuminemia). Kidney biopsies typically show the characteristic pattern of drug-induced acute interstitial nephritis (AIN): a diffuse interstitial infiltrate composed predominantly of T lymphocytes, although eosinophils, macrophages, and plasma cells can also be observed (7). The glomeruli are normal in light microscopy, but a diffuse effacement of podocyte foot processes is observed in electron microscopy (1–4). NSAIDs-related minimal change disease could be, therefore, categorized as a complication of NSAIDs-induced AIN. However, a "pure" nephrotic syndrome has been described in some patients taking NSAIDs, with diffuse fusion of foot processes but no accompanying interstitial infiltrates. In some patients, tubular necrosis without interstitial infiltrates has been the most salient histopathologic finding. Patients with AIN accompanied by minimal change disease have been reported with a variety of conventional NSAIDs and selective COX-2 inhibitors. As usual in NSAIDs-induced AIN, the extrarenal manifestations (low-grade fever, skin rash, and eosinophilia) that frequently accompany AIN induced by antibiotics and other drugs are characteristically absent (7). Although NSAIDs are one of the most frequent causes of drug-induced AIN, the incidence of nephrotic syndrome seems to be low. In two patient series of drug-induced AIN, only three patients of a total of 121 showed nephrotic-range proteinuria, although NSAIDs were the offending drug in 40% of the patients (7). However, patients with NSAIDs-related AIN tend to present higher proteinuria values than other types of drug-induced AIN, although they rarely reach the nephrotic range (7,8). Notably, nephrotic syndrome and nephrotic-range proteinuria seem to be a specific complication of NSAIDs, because they have been only exceptionally reported with other types of drug-induced AIN. To explain this susceptibility for proteinuria, it has been suggested that a decrease in the synthesis of prostaglandins induced by NSAIDs could result in an increased conversion of arachidonic acid to leukotrienes, which could activate T-helper cells and induce a diffuse podocyte damage. However, no studies have confirmed this hypothesis. In most patients, NSAIDs-related minimal change disease resolves after drug discontinuation, which is accompanied in some patients by a short course of corticosteroids (1–4). It has been reported that early treatment with corticosteroids can induce a more rapid and efficient recovery of kidney function in NSAIDs-induced AIN accompanied or not by nephrotic proteinuria (8). Paradoxically, NSAIDs induce a marked reduction of proteinuria in different types of nondiabetic glomerular nephropathies and can potentiate the antiproteinuric effect of renin-angiotensin blockers (9). Changes in glomerular hemodynamic through a preglomerular vasoconstriction and an improvement of the glomerular protein permselectivity have been invoked to explain this effect. However, the frequent side effects of NSAIDs have prevented their clinical use for the treatment of glomerular diseases. Nephrotic syndrome with a histopathologic pattern of membranous nephropathy, a paradigmatic type of immune complex glomerular disease, is another side effect of NSAIDs, and different types of conventional and selective NSAIDs have been reported as causatives of this complication (1,5,6). The presence of electron-dense subepithelial deposits along the glomerular capillary loops and a complete effacement of foot processes were the most characteristic findings in kidney biopsies (5,6). Unlike NSAIDs-related minimal change disease, inflammatory interstitial infiltrates were absent in most reported patients. This histologic difference explains why most of the patients with NSAIDs-induced minimal change disease present with nephrotic syndrome accompanied by severe AKI, whereas nephrotic syndrome with normal kidney function is the most frequent presentation in NSAIDs-induced membranous nephropathy. Immunostaining for the different subclasses of IgG can help to differentiate NSAIDs-induced membranous nephropathy from primary forms of the disease. As in other types of secondary membranous nephropathy, deposition of IgG1 has been reported in patients with cases associated with NSAIDs (5), whereas deposition of IgG4 is characteristic of primary forms. The pathogenesis of membranous nephropathy associated with NSAIDs is unknown. Glomerular deposition of antigens bound to NSAIDs could elicit an immune response, although these drugs could also exacerbate or trigger autoimmune reactions against podocyte antigens. Intriguingly, positive immunostaining for PLA2R has been reported in a patient with membranous nephropathy precipitated by piroxicam, although serum anti-PLA2R was not available (5). The incidence of NSAIDs-related membranous nephropathy could be greater than suspected according with the study of Radford et al. (6). They reported 125 patients with early membranous nephropathy (stages 1 and 2 membranous nephropathy with small subepithelial deposits). Twenty-nine of them were taking NSAIDs at the time of diagnosis, of which 13 (10%) fulfilled the criteria defined by the authors to establish the diagnosis of NSAIDs-related membranous nephropathy: onset of the nephrotic syndrome while taking NSAIDs, exclusion of other causes of secondary membranous nephropathy, and rapid disappearance of proteinuria after NSAIDs withdrawal (6). Interestingly and reinforcing the causal association between NSAIDs and nephrotic syndrome, relapses of proteinuria have been reported after re-exposure to NSAIDs, and in some patients, re-exposure was to a type of NSAIDs different from the one causing the first episode of nephrotic syndrome (5). In this issue of CJASN, Bakhriansyah et al. (10) describe the results of a systematic observational matched patient-control study about the association between NSAIDs and nephrotic syndrome. The study used data from the Clinical Practice Research Datalink, a general practitioner database of the United Kingdom National Health Service. Patients had a diagnosis of nephrotic syndrome established in the period 1989–2017, and controls were patients without nephrotic syndrome before and at the date of diagnosis of nephrotic syndrome in matching cases. Exposure to NSAIDs was divided into current use (NSAIDs prescription within the last month before the date of diagnosis), recent use (prescription within 1–2 months before), or past use (prescription >2 months before). According to the duration of NSAIDs exposure, current use was divided into use of 1–14, 15–28, or >28 days. Patients with past use were divided into those in whom NSAIDs had been discontinued between 2 months and 2 years before the date of diagnosis and those with an NSAIDs discontinuation >2 years. NSAIDs were classified as acetic acid derivatives (such as indomethacin, ketorolac, and diclofenac), propionic acid derivatives (such as naproxen, ibuprofen, and ketoprofen), selective COX-2 inhibitors (coxibs), fenamates, and oxicams, and other NSAIDs. A total of 2620 patients and 10,454 matched controls were included in the analysis. The results show that current use for >2 weeks, recent use, and past use (discontinuation >2 months to 2 years) of conventional NSAIDs (acetic acid and propionic acid derivatives) were associated with a significantly higher risk of nephrotic syndrome (adjusted odds ratio, 1.34; 95% confidence interval, 1.06 to 1.70; adjusted odds ratio, 1.55; 95% confidence interval, 1.11 to 2.15; and adjusted odds ratio, 1.24; 95% confidence interval, 1.07 to 1.43, respectively) compared with nonuse and that the risk disappeared after 2 years of discontinuation. The use of selective COX-2 inhibitors was not associated with a higher risk of nephrotic syndrome, although there was not a statistically significant trend among patients with a past use (>2 months to 2 years). This study is the first systematic analysis of the association between NSAIDs consumption and the risk of developing a nephrotic syndrome. Its conclusions are clinically relevant, although several important caveats should be taken into account. One of them is the inevitable chronological imprecision when analyzing drugs, like conventional NSAIDs, that are frequently available over the counter and consumed in a discontinuous manner by a large number of normal subjects. Additionally, the accuracy of the diagnosis of nephrotic syndrome using pre-established codes should be taken with caution in studies like this that involve a large number of patients over a long period of time. The criteria used to establish the diagnosis of nephrotic syndrome are not reported, and therefore, we do not know if all included patients presented a proteinuria >3.5 g/d accompanied by hypoalbuminemia. A major constraint of the study is the low percentage of patients with histologic confirmation of kidney disease. Although patients 18 years old or younger were excluded (another limitation of the study), a kidney biopsy was performed in only 11% of the patients, despite the fact that kidney biopsy is considered a central tool in the diagnostic workup of most adult patients presenting with nephrotic syndrome. The list of histologic diagnoses is somewhat surprising, because only a minority of patients (15 of 167) taking NSAIDs and presenting a nephrotic syndrome received the diagnosis of minimal change disease or AIN, and other diagnoses (for instance, crescentic or mesangiocapillary GN) have no apparent pathogenic relationship with these drugs. The study of Bakhriansyah et al. (10) raises questions of great clinical importance for the clinician. Are we overlooking patients with NSAIDs-induced nephrotic syndrome? If so, are we prescribing long courses of immunosuppressive treatments to patients with minimal change disease or membranous nephropathy caused by NSAIDs that would have resolved with the discontinuation of the drug accompanied perhaps by a short course of corticosteroids? Considering that the existing literature on this topic is in general old and scarce, with only patient reports or short series of patients published, data from this study should encourage nephrologists to, on one hand, carefully review the current or recent intake of NSAIDs in any patient with nephrotic syndrome, particularly when minimal change disease or membranous nephropathy is found in kidney biopsies, and on the other hand, perform collaborative studies to collect large series of patients with unequivocal diagnosis of NSAIDs-induced nephrotic syndrome to identify their differential clinical and histopathologic characteristics and delineate their more efficient treatment. Basic research about the pathogenic mechanisms through which NSAIDs cause glomerular damage is also needed. Disclosures Dr. Praga has received personal fees for lectures from Alexion, Fresenius, Otsuka, and Retrophin and grant support and personal fees from Alexion, outside of the submitted work. Dr. Mérida has nothing to disclose.

Background and Aims Nephrotic syndrome (NS) is a common indication for renal biopsy, and a frequent presenting clinical syndrome for certain glomerulonephritis (GN), particularly minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS) or membranous nephropathy (MN). However, less is known on the spectrum of clinicopathological diagnosis and characteristics in patients with nephrotic-range proteinuria without nephrotic syndrome (NRP). We aim to evaluate the differences in clinicopathological diagnosis and characteristics of patients with NS versus NRP. Method All patients who underwent a renal biopsy from the 1st January 2014 to 31st December 2016 were included in the study. Patients with no urine protein quantification, serum albumin or lipid panel done at the time of renal biopsy or no glomeruli seen on renal histology were excluded. Data for renal histopathology, clinical diagnosis and patient characteristics were obtained from review of medical records. Results A total of 362 patients underwent a renal biopsy from the 1st January 2014 to 31st December 2016. Of these, 76 patients had NS and 106 patients had NRP. Mean age was 51.1±17.0, 51.5% were male and 70.9% were Chinese. In the NS group, there were 25 (32.9%) MCD, 10 (13.2%) FSGS of which 8 were primary, 14 (18.4%) lupus nephritis (LN), 11 (14.5%) MN, 8 (10.5%) diabetic glomerulosclerosis, 2 (2.6%) Immunoglobulin A nephropathy (IgAN), 2 (2.6%) amyloidosis and 4 (5.3%) with other diagnoses (2 membranoproliferative GN, 1 acute interstitial nephritis, 1 chronic glomerulosclerosis). In the NRP group, there were 26 (24.5%) diabetic nephropathy, 21 (19.8%) IgAN, 15 (14.2%) LN, 13 (12.3%) FSGS of which 12 were secondary FSGS, 12 (11.3%) chronic glomerulosclerosis, 8 (7.5%) MN, 4 (3.8%) pauci-immune GN and 7 (6.6%) with other diagnosis (2 infection-related glomerulonephritis, 3 had mild chronic changes with proteinuria attributable to overflow proteinuria from myeloma, 1 Alport syndrome, 1 thrombotic microangiopathy). There were significantly more cases of primary GN in the NS group (63.2% versus 28.3%, p&amp;lt;0.001), while the NRP group had more secondary GN and non-GN cases. The most common cause of primary GN is MCD in the NS group and IgAN in the NRP group. LN is the most common secondary GN in both NS and NRP groups. There was no significant difference in age, gender and race between the NS and NRP group. The NS group had a significantly higher proteinuria (10.8±5.5 versus 6.3±3.5, p&amp;lt;0.001) and lower serum albumin (17.0±5.7 versus 28.0±7.6, p&amp;lt;0.001). The NRP group had significantly more patients with abnormal renal function at the time of biopsy (83 (78.30%) versus 39 (51.32%) patients, p&amp;lt;0.001), a higher mean systolic BP (144.1±26.3mmHg versus 134.2±26.2mmHg, p=0.014) and a higher percentage of diabetes mellitus (38 (35.85%) versus 15 (19.74%) patients, p=0.018) compared to the NS group. Conclusion The clinicopathological diagnosis between patients with NS and NRP differ significantly. Patients with NRP are more likely to have secondary glomerular disease or non-glomerular disease, with abnormal renal function and higher prevalence of hypertension and diabetes mellitus.

218: A Retrospective Study on the Mortality of Bone Marrow Transplant Recipients with Severe Acute Kidney Injury

Nephrotic Range Proteinuria in Renal Transplantation: Clinical and Histologic Correlates in a 10-year Retrospective Study

Background and Aims A full-house pattern at immunofluorescence (IF) in kidney biopsies is usually associated with Lupus Nephritis (LN). However, it can be also secondary to other causes, such as infections, or it can idiopathic, without a defined origin. Idiopathic Full House non-lupus Nephropathy (iFH-N) represents a rare entity previously identified in small cohorts of patients, with different clinical features and outcomes. A limited number of the described cases developed overt systemic lupus erythematosus (SLE) during follow up, while renal outcome varied across different studies. A retrospective observational study aimed at evaluating clinical presentation and outcomes of patients with iFH-N in a Tertiary Center has been performed. Long-term renal function and development of overt SLE have been considered as main outcomes of the study. Method All native kidney biopsies performed from January 2012 to December 2022 in our Institution were considered. Full-house pattern was defined as simultaneous positivity for IgG, IgM, IgA, C3 and C1q staining at IF. Inclusion criteria were: age ≥18, full-house pattern at kidney biopsy, patients not meeting criteria for SLE diagnosis according to American College of Rheumatology (ACR) 1997 classification or Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria. Exclusion criteria: diagnosis of SLE, secondary causes of full-house pattern at kidney biopsy. We considered histological, clinical and laboratory features, performed therapies, renal function and SLE development during follow up. Results In the considered period, 2110 patients underwent a native kidney biopsy at our Institution. Of these, 91 patients had a histological finding of full-house nephropathy and were initially included for further evaluation. Of the 91 patients, 84 had received a diagnosis of SLE and were excluded, while 7 did not meet the criteria for a diagnosis of SLE. Two of these 7 were further excluded, having a full house pattern secondary to other conditions. Five patients were finally labelled as iFH-N. At kidney biopsy, all 5 included subjects had a Membranous Nephropathy, with extracapillary proliferation in 2 cases. They were all females, 4 Caucasians (80%), 1 Black (20%). At presentation, mean age was 28.2 years (range 21–40). All had impairment of kidney function, 2 of 5 had a full-blown nephrotic syndrome, 3 of 5 a nephrotic range proteinuria. Mean serum creatinine was 2.1 mg/dl (SD± 0.47), mean eGFR 35.2 ml/min/1.73 m2 (SD ±11), mean proteinuria 7.1 gr/24 h (SD ±3.3). Antinuclear antibodies (ANA) were negative in 4 of 5 patients; anti-dsDNA, anti-extractable nuclear antigens (ENAs) and antiphospholipid antibodies were negative in all subjects; slightly low C3 was present in 3 of 5 subjects. All patients received immunosuppressive therapy, including high dose intravenous (iv) steroids in association with cyclophosphamide (CYC) or mycophenolate mofetil, or Intensified B Cell Depletion Protocol (i.e. iv steroids + CYC and Rituximab). Mean follow-up from the time of kidney biopsy was 7.4 year (SD ± 2.4) (range 3–10 years). During follow up, 4 patients (80%) developed end stage renal disease (ESRD) needing renal replacement therapy, 3 of them within 24 months after presentation. The two patients with crescents had a severe prognosis, starting dialysis within 10 months after presentation. The fifth patient developed chronic kidney disease stage 4. One patient formally developed an ACR negative, SLICC positive SLE two years after presentation, with new positivity for ANA and anti-dsDNA antibodies at high titer and low C3, in addition to renal involvement. Conclusion All patients with iFH-N had similar presentation, being all young females, with a Membranous Nephropathy, nephrotic proteinuria and impairment of kidney function. They all had an aggressive form of kidney disease, refractory to different regimens of immunosuppression and with poor long-term renal outcome. Only one case developed SLE on the long term, although without systemic signs. The relationship between idiopathic full-house nephropathy and SLE remains controversial.

Expression of nephrin, podocin and a-actinine-4 in renal tissue of patients with proteinuria

1 September 2009 Dear Editor, C1q nephropathy associated with deletion of long arm of chromosome 7 A 9-year-old boy with known chromosome 7q31.2-q32 deletion was referred with 6 months of asymptomatic microhaematuria and recent development of proteinuria, lethargy and anorexia. He was initially admitted to a regional hospital with a skin infection, and microhaematuria was incidentally detected, with raised anti-DNAse-B and anti-streptolysin-O titer. A urinary tract ultrasound was normal. He represented 2 months later with lethargy and anorexia. Urinalysis showed proteinuria and haematuria, with borderline hypertension (110/80). He was transferred to our service for further investigation, which yielded normal results for serum C3, C4, ANF, Anti-ds-DNA, UEC, FBP, plasma calcium, magnesium, phosphate and coagulation profile. A urine albumin/creatinine ratio was 73.2 (range <2.5) and calcium/creatinine ratio of 0.24 (0.04–0.70). Renal biopsy showed mesangioproliferative changes, normal tubulointerstitial pattern and no pathological vascular changes. Immunofluorescence revealed diffuse global, predominantly mesangial immunoglobulin G (IgG) and C3 deposition with extension into the capillary loops in some glomeruli. There was moderate C1q and sparse immunoglobin A (IgA) deposition (Fig. 1). Immunofluorescence shows moderate C1q and sparse IgA deposition, with diffuse global IgG and C3 deposition (predominantly mesangial) extending into the capillary loops of some glomeruli. Electron microscopy showed diffuse mesangial proliferation with extensive electron dense deposits in the mesangium and peripheral subepithelial basement membrane, with tubuloreticular inclusions. The histological findings in the absence of clinical, haematological and immunological signs of lupus was consistent with a diagnosis of C1q nephropathy. He has remained asymptomatic with no need for immunosuppression to date. This boy has previously been diagnosed with a de novo deletion of chromosome 7q31.2-32 by G-banded karyotype. He has learning problems, attention-deficit disorder with hyperactivity, seizures, dental abnormalities, a nephropathy and Wolf–Parkinson–White syndrome (WPWS). Previous published cases of deletions with similar breakpoints have language impairment because of Forkhead box protein P2 gene involvement, developmental delay and dysmorphic features,1 but there are no reports of nephropathy or WPWS with this deletion. No specific gene has been implicated in C1q nephropathy. Lim et al. reported a 3-year-old boy with C1q nephropathy and a family history of Dent disease, with the X-linked CLCN5 gene mutation. The significance of Dent disease to the development of the C1q nephropathy is unknown.2 Genes associated with proteinuria and nephrotic syndrome include NPHS1, NPHS2, WT1, LAMB2 and PLCE1. There are no known genes linked with nephrotic syndrome in the 7q region. The NOS3 gene in the 7q36 region has been implicated in causing hypertension and microalbuminaemia. Genetic regions on chromosomes 7q, 18q and 22q, contain genes determining variations in urinary albumin excretion, or susceptibility to proteinuria in families who have type 2 diabetes3 Whether the C1q nephropathy in our patient is related to the chromosome deletion remains to be elucidated. It is possible that this may be a chance observation. C1q nephropathy was first described in 1985 by Jennette and Hipp4 who outlined criteria for diagnosis as C1q deposits in the mesangium on immunofluorescence, corresponding mesangial or paramesangial electron-dense deposits on electron microscopy, and no evidence of systemic lupus erythematosus. The underlying aetiology is unknown. Children with C1q nephropathy commonly present with nephrotic syndrome or proteinuria. Kersnik et al. reported 12 paediatric patients: eight presented with nephrotic syndrome, one with nephrotic range proteinuria and three with non-nephrotic proteinuria associated with microhaematuria, hypertension and renal insufficiency.5 Vizjak et al. report on 72 C1q nephropathy patients (28 children). Clinical presentations included asymptomatic haematuria and or proteinuria (22%), frequently relapsing nephrotic syndrome with minimal change disease (63%) and nephrotic syndrome in all focal segmental glomerular sclerosis (FSGS) patients.6 Hatae et al.4 examined the results of 2221 children aged 1–15 years who underwent renal biopsy between 1975 and 2002. Thirty were diagnosed with C1q nephropathy based on the criteria of Jennette and Hipp. The C1q patients were divided into asymptomatic urinary abnormalities (18) and nephrotic group (12). Light microscopy showed minimal change disease (MCD) in 73%, mesangial proliferative glomerulonephritis in 20%, and FSGS in 7%. The natural history of C1q nephropathy in children suggests a good prognosis where the histological findings are of MCD, while children with FSGS progress to end-stage disease. Children with C1q nephropathy presenting with nephrotic syndrome are less likely to respond to corticosteroids and relapse frequently.4, 6 In summary, this is the first report noting an association between a deletion on the long arm of chromosome 7 and C1q nephropathy, suggesting that the relationship needs to be further investigated if other cases are identified. The authors are grateful to Dr TJ Beattie (Renal Unit, Royal Hospital for Sick Children – Yorkhill, Glasgow, Scotland) for his editorial suggestions.

BACKGROUND AND AIMS Minimal change lesion (MCD) accounts for 10–15% of adult patients with nephrotic syndrome and is characterized by edema, nephrotic-ranged proteinuria (NP) and pathologic findings of nearly normal appearance of glomeruli on light microscopy, minimal staining of immunoglobins and extensive effacement of foot process of the podocyte. However, the fate of MCD with typical pathologic findings without nephrotic proteinuria (Non-NP) needs to be defined in more details. METHOD We enrolled 79 adult MCD patients with the first renal biopsy in a tertiary teaching hospital from May 2003 to June 2017. We did not include patients having any immunosuppressive treatment before renal biopsy, patients with inappropriate biopsy samples (&amp;lt;10 glomeruli/biopsy, any electron dense deposit, and light microscopic findings suggestive of secondary causes). Remission of proteinuria was defined as urine protein-to-creatinine ratio (UPCR) &amp;lt; 0.3 g/g creatinine and recurrence of proteinuria as UPCR ≥ 3.0 g/g creatinine. We compared the clinic-pathologic features of MCD with or without NP at admission for renal biopsy, the frequency of flare to nephrotic proteinuria and the renal failure which was defined as decrease of estimated glomerular filtration rate (GFR) more than 50% compared to GFR at renal biopsy, GFR less than 15 mL/min/1.73 m2 or progressed to end-stage renal disease during follow-up period. RESULTS There were 3 patients with UPCR &amp;lt; 0.3 g/g creatinine, 17 patients with UPCR 0.3–2.9 g/g creatinine and 59 patients with UPCR ≥ 3.0 g/g creatinine at admission for renal biopsy. Mean age at renal biopsy was 53.7 ± 19.2 (range:18.5–99.0) years, and there were 38 male patients (48.1%). Non-NP group had lower UPCR (1.36 ± 0.99 versus 10.2 ± 6.21 g/g creatinine, P &amp;lt; .001) and higher GFR (98 ± 27 versus 75 ± 36 mL/min/1.73 m2 P = .012) at renal biopsy, and lower frequency of acute kidney injury during follow-up period [1/20 (5.0%) versus 35/59 (59.3%) patients, P &amp;lt; .001]. NP group showed more severe foot process effacement and interstitial changes. Other clinic-pathologic findings were not different between groups. During follow-up period (63.2 ± 50.4 months), eight patients (40.0%) had recurrence of proteinuria and nine patients (45.0%) had steroid treatment in non-NP group. Among NP group, 55 patients (93.2%) had been treated by steroid. The peak dose of prednisolone for patients having steroid treatment was not different between groups (Non-NP versus NP: 0.92 ± 0.16 mg/kg/day versus 0.88 ± 0.17 mg/kg/day, P = .491). The remission rate by the first treatment of steroid was not different between groups (non-NP versus NP: 9/9 versus 50/55, P = 1.000). The recurrence of proteinuria was developed in 8/9 non-NP patients (88.9%) and in 25/50 (50.0%) NP patients after the first remission of proteinuria by steroid treatment (P = .282). Recurrence of proteinuria was developed 0.23 ± 0.33 times/year in Non-NP group and 0.25 ± 0.41 times/year in NP group (P = .830). At the last follow-up period, the final remission rate of proteinuria was not different [65.0% of non-NP patients (17/20) versus 76.5% of NP patients (45/59), P = .384], and the rate of renal failure was not different, neither [15.0% of non-NP patients (3/20) versus 27.1% of NP patients (16/59), P = .371]. CONCLUSION The adult MCD patients with non-nephrotic-ranged proteinuria at renal biopsy showed similar clinical outcomes compared with patients with nephrotic-ranged proteinuria. Therefore, the MCD pathology should be paid more attention regardless of the amount of proteinuria at renal biopsy.

It is thought that a large amount of albumin leaking from the glomerulus in nephrotic syndrome (NS) is reabsorbed at the proximal tubule and catabolized. Therefore, it is possible the final quantity of urinary protein does not always reflect the amount of leakage of protein from the glomerulus. We experienced two cases without nephrotic range proteinuria thought to involve hypoproteinemia due to the same pathophysiology as NS. On these patients, we performed protein leakage scintigraphy with technetium-99m human serum albumin diethylenetriamine pentaacetic acid (99mTc-HSAD) to exclude a diagnosis of protein-losing gastroenteropathy and observed diffuse positive accumulation in the kidneys with more intense uptake in the kidney than the liver on the anterior view 24 hours after 99mTc-HSAD administration. In healthy adults intravenously given 99mTc-HSAD, the same dynamics are observed as in albumin metabolism, and the organ radioactivity of the liver and kidneys after 24 hours is equal. Therefore, we thought it was possible that the renal uptake 24 hours after 99mTc-HSAD administration was a characteristic finding of NS. In order to confirm it, the subjects were divided into two groups: the NS group (n = 10) and the non-NS group (n = 7). We defined more intense uptake in the kidney than the liver on the anterior view 24 hours after 99mTc-HSAD administration as Dense Kidney (+). Furthermore, we designed regions of interest in the right and left kidneys and liver on anterior and posterior images, then calculated the kidney-liver ratio. Nine of the ten patients had Dense Kidney (+) in the NS group, compared to none in the non-NS group. And the kidney-liver ratio was significantly higher in the NS group than in the non-NS group on each view in the bilateral kidneys. In conclusion, our results suggest that the renal uptake 24 hours after 99mTc-HSAD administration is a characteristic finding of NS.

Background:Immunoglobulin A nephropathy (IgAN) with nephrotic syndrome is an uncommon form of IgAN. Clinical and morphological characteristics of proteinuria in IgAN, especially when is in nephrotic range have not yet been fully examined. This study was aimed to correlate morphologic variables of the Oxford classification, and various clinical data with proteinuria in IgAN patients. We also aimed to demonstrate the significance of prevention of proteinuria as one of the important factors in progression of this disease.Methods:In an observational study conducted on IgAN patients, total of 114 biopsies were entered in the study. IgAN was diagnosed by light and immunofluorescence study.Results:Of 114 patients 70.2% were male. Mean age of patients was 37.7 ± 13.6 years. The mean of proteinuria was 1742 ± 1324 mg/day. Also mean of serum creatinine (Cr) was 1.6 ± 1.5 mg/dL. Of 114 patients, 11(9.6%) had nephrotic range proteinuria. In this study, there was a positive correlation between proteinuria and serum Cr, peri-glomerular fibrosis or interstitial fibrosis. There was a positive association between proteinuria and totally sclerotic glomeruli too. There was also a positive association between the amount of fibrous crescents and the level of proteinuria. Nephrotic proteinuria could just be seen in male patients. Also, nephrotic syndrome had a positive association with the number of crescents.Conclusions:Our findings firstly support the prognostic value of crescent due to its association with proteinuria and secondly imply the importance of treatment of proteinuria to prevent progression of IgAN.