Diffuse Proliferative Glomerulonephritis Research Articles

Renal Manifestation of Mixed Connective Tissue Disease

Abstract A young female presented with facial puffiness and swelling in both lower limbs for 3 months, distension of the abdomen, and breathlessness on exertion for 1 month with a history of hypertension and hypothyroid on regular treatment. On general physical examination, there were pallor, bilateral pitting edema, tachycardia, and blood pressure of 190/100 mmHg. Abdominal examination revealed shifting dullness. Respiratory and cardiovascular systems were normal. Fundoscopy revealed Grade 1 papilledema, and the rest of the neurological examination was unremarkable. Investigations showed normocytic normochromic anemia, serum creatinine of 1.6 mg/dl, and hypoalbuminemia; urine R/E showed significant proteinuria; and anti-U1 ribonucleoprotein particle antibodies were positive. Two-dimensional echocardiography showed mild concentric left ventricular hypertrophy and mild pericardial effusion. Ultrasonography abdomen showed bilateral renal parenchymal disease and moderate ascites. Renal biopsy revealed diffuse proliferative glomerulonephritis and lupus nephritis Class IV. Renal manifestation is very rare in mixed connective tissue disease as an initial presentation

Mutation of NPHS1, NPHS2, WT1, LAMB2, COL4A5 and other genes in children with idiopathic steroid resistant nephrotic syndrome

Background: Many children with idiopathic steroid resistant nephrotic syndrome have been reported worldwide due to mutation of NPHS1, NPHS2, WT1 and LAMB2 genes. This study aimed to determine the frequency of mutation of NPHS1, NPHS2, WT1, LAMB2, COL4A5 and other genes and their association with renal histopathological patterns of idiopathic steroid resistant nephrotic syndrome patients. Methods: This cross-sectional study was conducted on 25 patients with idiopathic steroid resistant nephrotic aged 1-17 years in the Department of Paediatric Nephrology, Bangabandhu Sheikh Mujib Medical University, Bangladesh, from July 2017 to June 2018. Next Generation Sequencing and mutation analysis were performed after DNA extraction from patients' venous blood lymphocytes. Histopathological study of renal tissue was done among 17 patients. Results: A little more than half (56%) of the patients were male. The mean age at the initial attack of nephrotic syndrome was 94.2 months. They mostly had minimal change disease (41%) and IgA nephropathy (12%). One subject had the NPHS2 gene mutation, histopathologically diffuse mesangial proliferative glomerulonephritis, and clinically stage-4 chronic kidney disease. Another subject had the COL4A5 gene mutation and focal segmental glomerulosclerosis. Both were male and had no familial renal disease, consanguinity, or hematuria. Conclusion: Children with idiopathic steroid resistant nephrotic syndrome showed NPHS2 and COL4A5 gene mutations. Histopathologically, they showed diffuse mesangial proliferative glomerulonephritis and focal segmental glomerulosclerosis.

Goodpasture Syndrome with Neurological Condition Associated with anti-MBG Ab, Negative ANCA: Case Report

Goodpasture syndrome is a rare immunologically based clinical entity that is characterized by rapidly progressive glomerulonephritis, diffuse pulmonary hemorrhage, and the presence of circulating autoantibodies against the glomerular basement membrane (GBM). Concomitant central nervous system (CNS) manifestations are an unusual presentation of GSP in the absence of ANCA. We present a case of atypical course of the disease in a 48-year-old female patient who started with the presence of hemoptoic sputums and manifestations of uremic syndrome in the presence of high titres of glomerular basement anti membrane antibodies (Ac-anti-MBG) and negative ANCA, with a report of diffuse active extracapillary proliferative glomerulonephritis biopsy, of the pauciimmune type. After immunosuppressive treatment and plasmapheresis, the patient presented decreased anti-MBG Ab titres, as well as improvement of symptoms, however without recovery of renal function on hemodialysis, after 2 months he presents clonic-tonic seizures crisis, we conclude that PGS with neurological involvement is extremely rare, especially with negative ANCAs.

#2691 GLOMERULAR LESIONS IN PATIENTS WITH ANTIPHOSPHOLIPID SYNDROME

Abstract Background and Aims Antiphospholipid syndrome (APS) is a complex autoimmune systemic disease, characterized by the presence of circulating antibodies directed against anionic phospholipids and the protein bound to them (aPL), leading to recurrent thrombosis and/or obstetrical complications. Renal manifestation of antiphospholipid syndrome conform a wide spectrum of disease renal syndrome. APS nephropathy (APSN) is considered a renal small-vessels vasculopathy, that can present acutely or chronically. The aim of the study is to identify glomerular lesions in patients with APSN. Method We studied retrospectively 114 patients (51 male, 63 female; age between 19 and 58 years; duration of follow-up was between 2 and 16 years) fulfilling classification criteria for APS. Renal and extra-renal symptoms were analyzed. None of the patients developed SLE in follow up. 18 patients with evidence of renal involvement underwent renal biopsy. All cases had proteinuria and five of them presented nephrotic syndrome. Results Of 18 patients with kidney biopsy, 8 (44,44%) were male and 10 (55,56%) - female. Four of patients with renal biopsy had membranous glomerulonephritis, two had diffuse proliferative glomerulonephritis, 2 - mesangial C3 nephropathy, 2 - minimal change disease, 1- focal segmental glomerulosclerosis, the other seven had classic pathologic findings consistent with APSN. Chronic lesions with fibrous intimal hyperplasia being the most common. Thrombotic microangiopathy (TMA) in glomeruli was characterized by fibrin thrombi without inflammatory cells or immune complexes. Double contour of the glomerular basement membrane was associated with mesangiolysis and endothelial cell swelling in 5 patients with APSN. Electron microscopy confirmed subendothelial edema. Segmental glomerulosclerosis was observed in 4 patients. Tubulointerstitium was injured with interstitial fibrosis and tubular atrophy. Patients with APS and renal involvement were older (p<0,05), had LA positive test (p<0,005) and low complement levels (p<0,05). Hypertension is present in all cases with APSN, reduced glomerular filtration rate – in 4. All cases had proteinuria and five of them presented with nephrotic syndrome. Microscopic hematuria is observed in 4 patients. The treatment of APSN includes standard anticoagulant treatment for APS, inhibitors of the angiotensin system in patients with hypertension and proteinuria, steroids, intravenous immunoglobulin, cyclophosphamide and azathioprine. Conclusion Of 18 patients with kidney biopsy, 8 (44,44%) were male and 10 (55,56%) - female. Four of patients with renal biopsy had membranous glomerulonephritis, two had diffuse proliferative glomerulonephritis, 2 - mesangial C3 nephropathy, 2 - minimal change disease, 1- focal segmental glomerulosclerosis, the other seven had classic pathologic findings consistent with APSN. Chronic lesions with fibrous intimal hyperplasia being the most common. Thrombotic microangiopathy (TMA) in glomeruli was characterized by fibrin thrombi without inflammatory cells or immune complexes. Double contour of the glomerular basement membrane was associated with mesangiolysis and endothelial cell swelling in 5 patients with APSN. Electron microscopy confirmed subendothelial edema. Segmental glomerulosclerosis was observed in 4 patients. Tubulointerstitium was injured with interstitial fibrosis and tubular atrophy. Patients with APS and renal involvement were older (p<0,05), had LA positive test (p<0,005) and low complement levels (p<0,05). Hypertension is present in all cases with APSN, reduced glomerular filtration rate – in 4. All cases had proteinuria and five of them presented with nephrotic syndrome. Microscopic hematuria is observed in 4 patients. The treatment of APSN includes standard anticoagulant treatment for APS, inhibitors of the angiotensin system in patients with hypertension and proteinuria, steroids, intravenous immunoglobulin, cyclophosphamide and azathioprine.

Kidney and urinary tract involvement in systemic mastocytosis.

Systemic mastocytosis (SM) is a disorder of excessive mast cell accumulation in tissues due to a somatic gain-of-function mutation, commonly in the KIT gene, which prevents apoptosis of mast cells. Whereas bone marrow, skin, lymph nodes, spleen, and gastrointestinal tract are commonly involved, kidneys are rarely involved directly by SM. However, there are increasing reports of indirect kidney involvement in patients with SM. Novel anti-neoplastic agents to treat advanced forms of SM include non-specific tyrosine kinase inhibitors, which are reported to be associated with kidney dysfunction in some patients. SM is also associated with immune-mediated glomerulonephritis (GN) like mesangioproliferative GN, membranous nephropathy, and diffuse proliferative GN. Kidney injury, in the form of monoclonal deposition disease and primary light chain amyloidosis, is reported in SM associated with plasma cell dyscrasia. In this narrative review, we discuss the various ways kidneys (and the urinary tract) are involved in patients with SM.

Heterogeneity in Kidney Histology and Its Clinical Indicators in Type 2 Diabetes Mellitus: A Retrospective Study

We analyzed the clinical profile and kidney biopsy of a total of 66 type 2 diabetes patients. Based on kidney histology, they were divided into-Class I (Diabetic Nephropathy), Class II (Non-diabetic kidney disease), and Class III (Mixed lesion). Demographic data, clinical presentation, and laboratory values were collected and analyzed. This study tried to examine the heterogeneity in kidney disease, its clinical indicator, and the role of kidney biopsy in the diagnosis of kidney disease in diabetes. Class I consisted of 36(54.5%), class II 17(25.8%), and class III 13(19.7%) patients. The commonest clinical presentation was nephrotic syndrome 33(50%) followed by chronic kidney disease 16(24.4%) and asymptomatic urinary abnormality 8(12.1%). Diabetic retinopathy (DR) was present in 27(41%) cases. DR was significantly higher in the class I patients (p < 0.05). Specificity and positive predictive values of DR for DN were 0.83 and 0.81, respectively (sensitivity 0.61; negative predictive values 0.64). The Association of the duration of diabetes and the level of proteinuria with DN was statistically not significant (p > 0.05). Idiopathic MN (6) and Amyloidosis (2) were the most common isolated NDKD; whereas diffuse proliferative glomerulonephritis (DPGN) (7) was the commonest NDKD in mixed disease. Another common form of NDKD in mixed disease was Thrombotic Microangiopathy (2) and IgA nephropathy (2). NDKD was observed in 5(18.5%) cases in presence of DR. We noted biopsy-proven DN even in 14(35.9%) cases without DR, in 4(50%) cases with microalbuminuria and 14(38.9%) cases with a short duration of diabetes. Almost half (45%) of cases with atypical presentation have non-diabetic kidney disease (NDKD), though even among these cases with atypical presentation diabetic nephropathy (either alone or in mixed form) is commonly seen in 74.2% of cases. DN has been seen in a subset of cases without DR, with microalbuminuria, and with a short duration of diabetes. Clinical indicators were insensitive in distinguishing DN Vs NDKD. Hence, a kidney biopsy may be a potential tool for the accurate diagnosis of kidney disease.

Pediatric Glomerular Diseases in North India-Epidemiology and Clinicopathologic Correlation.

Glomerular diseases vary with age, and it is important to investigate the spectrum of glomerular diseases in pediatric patients to help in a more precise clinical diagnosis and optimize the management of patients. We aimed to study the clinicopathologic pattern of pediatric glomerular diseases in North India. This is a 5-year retrospective, single-center cohort study. The database was searched to identify all pediatric patients with glomerular diseases in their native kidney biopsies. About 2890 native renal biopsies were studied, of which 409 were pediatric glomerular diseases. The median age was 15 years with a male preponderance. Nephrotic syndrome was the most common presentation (60.8%), followed by non-nephrotic proteinuria with hematuria (18.5%), rapidly proliferative glomerulonephritis (7%), isolated hematuria (5.3%), acute nephritic syndrome (3.4%), non-nephrotic proteinuria (1.9%), and advanced renal failure (0.7%). Minimal change disease (MCD) was the most common histological diagnosis, followed by focal segmental glomerulosclerosis (17.4%), IgA nephropathy (IgAN; 10%), membranous nephropathy (6.6%), lupus nephritis (5.9%), crescentic glomerulonephritis (2.9%), and C3 glomerulopathy (2.9%). Diffuse proliferative glomerulonephritis (DPGN) was the most common histological diagnosis in patients with hematuria and non-nephrotic as well as nephrotic range proteinuria. The most common histological diagnoses for isolated hematuria and acute nephritic syndrome were IgAN and postinfectious glomerulonephritis (PIGN), respectively. MCD and lupus nephritis are the most common pediatric primary and secondary histopathologic diagnoses, respectively. The adolescent-onset glomerular diseases have a higher frequency of IgAN, membranous nephropathy, and DPGN. PIGN is still an important differential in our pediatric patients presenting with acute nephritic syndrome.

Successful treatment of infectious endocarditis-associated glomerulonephritis during active hepatitis C infection: a case report

BackgroundHepatitis C virus (HCV) may play a pathogenic role in several forms of immune complex glomerulonephritis (GN). We present a patient whose initial clinical presentation instilled suspicion of HCV-related renal involvement. Yet, histopathologic data oriented towards a different diagnosis.Case presentationA 68-year old man presented with kidney dysfunction, cryoglobulins, low C4 level, high HCV—RNA and cutaneous vasculitis. The first hypothesis was a hepatitis C-related cryoglobulinemic glomerulonephritis. Renal biopsy revealed endocapillary and mesangial cells hypercellularity with complement C3 and IgM deposits. The echocardiography showed an infectious endocarditis (IE) on aortic valve. Appropriate antibiotic therapy and a prosthetic valve replacement were performed, obtaining recovery of renal function.ConclusionHCV infection may be linked to multiple renal manifestations, often immune-complex GN such as cryoglobulinemic membrano-proliferative GN. Renal disease due to IE is usually associated to focal, segmental or diffuse proliferative GN, with prominent endocapillary proliferation. The most common infectious agents are Staphylococcus aureus and Streptococcus species.This case report may be relevant because the renal dysfunction was highly suggestive of a cryoglobulinemic GN on a clinical ground, but the histologic pattern after performing the renal biopsy oriented towards a different cause of the underlying disease, that required a specific antibiotic treatment. The renal biopsy is always required to confirm a clinical suspicious in patients affected by multiple comorbidities.

Clinicopathological Analysis of Biopsy-Proven Glomerulonephritis in the Pediatric Patients : A Study from Tertiary Care Centre

Objective: To evaluate the clinic-pathological characteristics and their association with biopsy-proven glomerulonephritis in pediatric patients.&#x0D; Study Design: Prospective longitudinal study.&#x0D; Place and Duration of Study: Pediatric Department Nishtar Medical University, Multan Pakistan, from Jan 2014 to Dec 2019.&#x0D; Methodology: During the study, a total of 211 renal biopsy reports of different age groups were studied and analyzed for clinic-pathological features and patterns of direct immunofluorescence.&#x0D; Results: The mean age of 8.6±3.25 years was observed. The most common pathology was focal segmental glomerulo-sclerosis in 86 (40.76) of the patients, followed by mesangio-proliferative glomerulonephritis in 41 (19.43) of the patients. Minimal change disease was seen in 26 (12.32) cases. It was observed that the majority of the patients with diffuse proliferative glomerulonephritis were younger than 11 years old, whereas; 10 (11.2), patients with lupus nephritis, 11 (15.1) and membranous nephropathy, 10 (12.2) were comparatively older.&#x0D; Conclusion: Glomerulonephritis presents a diversified group of diseases with overlapping clinic-pathological features. The present study has reported many significant characteristics which could help diagnose a particular disorder among the pediatric population.

POS-058 CLINICAL OUTCOMES IN IRGN - A SINGLE CENTRE EXPERIENCE IN 21 PATIENTS FROM SOUTH INDIA

IRGN is one of the common causes of glomerulonephritis in India with a changing spectrum of clinical presentation and variable course. The most classical description of Light microscopy is diffuse endocapillary proliferative exudative Glomerulonephritis, but other findings of Light microscopy can also be found.

Acute Post-Streptococcal Glomerulonephritis in Children: A Comprehensive Review.

Acute post-streptococcal glomerulonephritis (APSGN) is an immune- complex (ICs) mediated glomerular disease triggered by group A β-hemolytic streptococcus (GAS) or Streptococcus pyogenes infections. APSGN represents a major cause of acquired kidney injury in children. This non-systematic review summarizes recent evidence on APSGN. We discuss the epidemiology, pathogenesis, clinical and laboratory findings, histopathology, treatment and prognosis of the disease. The median APSGN incidence in children in developing countries is estimated at 24.3/100,000 per year, compared with 6.2/100,000 per year in developed countries. Nephritis-associated plasmin receptor, identified as glyceraldehyde-3-phosphate dehydrogenase, and the cationic cysteine proteinase streptococcal pyrogenic exotoxin B are thought to be two leading streptococcal antigens involved in the pathogenesis of APSGN, which activate the complement system, mainly via the alternative but also the lectin pathway. This process is critical for the generation of inflammation by the ICs deposited in the glomerulus. The classic phenotype is an acute diffuse proliferative glomerulonephritis leading to features of the nephritic syndrome, including hematuria, oliguria, hypertension and edema. The histopathology shows that the glomeruli are diffusely affected, mostly presenting enlarged glomerular tuffs due to hypercellularity. Proliferative endothelial and mesangial cells and inflammation have also been observed. APSGN frequently has spontaneous recovery. There is no specific therapy, but its morbidity and mortality are drastically reduced by the prevention and/or treatment of complications. Despite recent advances, the pathogenesis of APSGN is not fully understood. There is no specific treatment for APSGN. The prognosis is generally good. However, some cases may evolve into chronic kidney disease.

Daily Hemodialysis Helps Critical Nephritic Lupus Patient: A Case Report

Background: Nephritic lupus is the most common and serious complication of systemic lupus erythematosus (SLE) and is associated with a worse prognosis. Hemodialysis is effective in alleviating symptoms and renal involvement in a nephritic lupus patient.&#x0D; Method: A 33-year-old female was diagnosed with SLE in September 2017. She was also diagnosed with diffuse membranous proliferative glomerulonephritis, as confirmed with a kidney biopsy. She complained of gradual onset limb weakness and peripheral edema 3 months before admission. She was treated with 6 cycles of cyclophosphamide and continued with methylprednisolone 16 mg once daily, hydroxychloroquine 200 mg once daily, and myfortic 360 mg twice daily. A day before ICU admission, her creatinine level was increased to 4.6 mg/dl with an estimated GFR of 12 ml/min and her symptoms then worsened into seizures and lung edema. Daily hemodialysis with heparin-free SLEDD was performed. About 2L was extracted for the first 6 hours with Qb 150 ml and Qd 300 ml and was continued until the day after. For the next 4 days, 3L was extracted per day with Qb 200ml and Qd 500 ml. The patients’ hemodynamic status was within normal limits during dialysis period. The condition improved and the patient was transferred to the ward.&#x0D; Discussions: Hemodialysis is a way to solve kidney problems in in nephritic lupus and SLE patients in general. It should not only be employed for mainly kidney problems but could be beneficial in autoimmune patients with conditions such as nephritic lupus. Slowly extracted dialysis type would be a good and inexpensive option to resolve nephritic lupus in compromising lupus patients. Filtration is ensured and solute removal is achieved relatively equivalent to CRRT.&#x0D; Conclusion: Daily hemodialysis could increase renal salvation by providing less creatinine serum and removing accumulated fluids. The SLEDD type could be used for critical nephritic lupus patients with reduced hemodynamic perturbations, minimal anticoagulant, and lower cost.

A clinical study of mycophenolate mofetil combined with low-dose steroids in the management of pediatric systemic lupus erythematosus

Purpose: To investigate the efficacy and safety of mycophenolate mofetil (MMF) combined with lowdose steroids in the treatment of pediatric systemic lupus erythematosus (pSLE).Methods: A total of 76 children were diagnosed and admitted with SLE, lupus nephritis (LN) and type IV diffuse proliferative glomerulonephritis at Hainan Women and Children’s Medical Center, Haikou, China from March 2017 to December 2018, had their clinical data analyzed retrospectively. Among them, 38 children received methylprednisolone pulse combined with MMF and intermittent oral low-dose glucocorticoids (GC), labelled MMF group, while the remaining 38 children, which served as control group, were treated with oral GC and transitional reduction. Pertinent biochemical parameters were evaluatedResults: Compared with control group, MMF group showed a notably lower level of erythrocyte sedimentation rate (ESR), a higher level of complement C3, lower level of serum creatinine (Scr) and 24-h urine protein level 6 months after treatment (p &lt; 0.05). Albumin level was higher in MMF group at 6 months and 12 months after treatment than in the control group. Compared to control group, the SLEDAI score in MMF group was significantly lower at 6 months and 12 months after treatment (p &lt; 0.05). Body mass index, triglyceride, fasting blood glucose and intraocular pressure levels in the MMF group were significantly lower than those in the control group (p &lt; 0.05). Post-treatment, peripheral blood CD3+ and CD4+ T lymphocytes, CD4+/CD8+ ratio and NK cell levels in the two groups were significantly increased, while CD8+ T lymphocyte level declined.Conclusion: MMF combined with low-dose methylprednisolone controls symptoms early and mitigates renal injury in the treatment of pSLE. It is also safe, and effectively regulates the patient's cellular immune function.

Histological Spectrum of Clinical Kidney Disease in Type 2 Diabetes Mellitus Patients with special Reference to nonalbuminuric Diabetic Nephropathy: A Kidney Biopsy-based Study.

Diabetic nephropathy (DN) is an important and catastrophic complication of diabetes mellitus (DM). Kidney disease has heterogeneity in histology in diabetes patients and includes both diabetic kidney disease (DKD) (albuminuric or nonalbuminuric) and nondiabetic kidney disease (NDKD) either in isolation or in coexistence with DN. Diabetic nephropathy is hard to overturn. While NDKD is treatable and reversible. We enrolled a total of 50 type 2 diabetes mellitus (T2DM) patients with clinical kidney disease, of both genders and age &gt;18 years, who underwent kidney biopsy from October 2016 to October 2018. Patients with proteinuria &lt;30 mg per day were excluded from the study. The indications of the renal biopsy were nephrotic syndrome (NS), active urinary sediment, rapid decline in renal function, asymptomatic proteinuria, and hematuria. A total of 50 (males: 42 and females: eight) patients with T2DM who underwent kidney biopsy were enrolled. The clinical presentation was: NS 26 (52%), chronic kidney disease (CKD) 11 (22%), asymptomatic proteinuria and hematuria six (12%), acute kidney injury (AKI) four (8%), and acute nephritic syndrome (ANS) three (6%). Diabetic retinopathy (DR) was noted in 19 (38%) cases. Kidney biopsy revealed isolated DN, isolated NDKD, and NDKD superimposed on DN in 26 (52%), 14 (28%), and 10 (20%) cases, respectively. Idiopathic membranous nephropathy (MN) (4) and amyloidosis (2) were the most common forms of NDKD, whereas diffuse proliferative glomerulonephritis (DPGN) was the main form of NDKD superimposed on DN. Diabetic nephropathy was observed in 15 (79%) cases in presence of DR and also in 11 (35.5%) cases even in absence of DR. Of eight patients with microalbuminuria four (50%) cases have biopsy-proven DN. About 48% of patients had NDKD either in isolation or in coexistence with DN. Diabetic nephropathy was found in absence of DR and in patients with a low level of proteinuria. The level of proteinuria and presence of DR does not help to distinguish DN vs NDKD. Hence, renal biopsy may be useful in selected T2DM patients with clinical kidney disease to diagnose NDKD.

Bartonella endocarditis and diffuse crescentic proliferative glomerulonephritis with a full-house pattern of immune complex deposition

BackgroundBartonella endocarditis is often a diagnostic challenge due to its variable clinical manifestations, especially when it is first presented with involvement of organs other than skin and lymph nodes, such as the kidney.Case presentationThis was a 13-year-old girl presenting with fever, chest and abdominal pain, acute kidney injury, nephrotic-range proteinuria and low complement levels. Her kidney biopsy showed diffuse crescentic proliferative glomerulonephritis with a full-house pattern of immune complex deposition shown by immunofluorescence, which was initially considered consistent with systemic lupus erythematous-associated glomerulonephritis (lupus nephritis). After extensive workup, Bartonella endocarditis was diagnosed. Antibiotic treatment and valvular replacement surgery were undertaken with subsequent return of kidney function to normal range.ConclusionThis case demonstrates the importance of considering the full clinical picture when interpreting clinical, laboratory and biopsy findings, because the treatment strategy for infective endocarditis versus lupus nephritis is drastically different.

MO248: A Renal Biopsy Might be a Mandatory Procedure in Patients with Hypertension and Decreased Renal Function Despite Normal Urinalysis Findings

Abstract BACKGROUND AND AIMS The most common cause of the end-stage renal disease is diabetes and hypertension. However, most centers do not try to find the cause of hypertension in patients with early-stage CKD but give antihypertensive medicine because most centers regard the cause as essential hypertension. Since blood pressure is regulated by the kidneys, we tried to find the cause of hypertension related to kidney disease. METHOD We carried out a single-center retrospective analysis of 1440 kidney biopsies performed for 8 years at a single center in Korea. All cases were done at the OPD level without admission, of which 367 cases (25.5%) showed hypertension/early-stage CKD with normal urinary findings at the time of renal biopsy. RESULTS The results are as follows in order of frequencies: IgA nephropathy (32.7%), mild focal nonspecific glomerulonephritis (GN) (17.7%), focal segmental glomerulosclerosis (FSGS) (15.3%), diffuse mesangial proliferative GN (12.8%), interstitial nephritis with tubular atrophy (7.6%), podocyte disease (3.3%) and membranous nephropathy (1.9%), and others include lupus nephritis, membranoproliferative GN, C1q nephropathy, C3GN, malignant hypertension (1.4%), etc. Most patients (95%) with hypertension/early-stage CKD were associated with chronic glomerulonephritis. Most patients with serious glomerular disease that may progress to ESRD, such as IgAN, FSGS and diffuse mesangial proliferative glomerulonephritis, have improved by aggressive immunotherapy. CONCLUSION In conclusion, before considering antihypertensive medicine in patients with early-stage CKD, a renal biopsy might be a mandatory procedure to save the kidney because more than 90% of cases are associated with glomerular disease.

G Protein‐coupled Estrogen Receptor 1 and Pregnancy Confer Protection against Renal Injury in Aged Female Mice

Chronic kidney disease, which is a leading risk factor impacting 1 in 7 American women, is more frequent in aged compared to younger women. Along with the natural aging process, aged women undergo a decline in circulating estrogen level, which is a predisposing factor for renal disease. Estrogen activates the G protein‐coupled estrogen receptor 1 (GPER1), which elicits cardiovascular and renal protective actions. Additionally, pregnancy augments GPER1‐induced vasodilation in rats. However, there is limited information on the potential interaction between GPER1 and pregnancy in the renal health later in life. We hypothesize that GPER1 signaling, and pregnancy confer protection against renal injury in aged female mice. In our study, 14‐16 months‐old GPER1 knock‐out (KO) and wild‐type (WT) female mice with and without a history of former pregnancies were placed into metabolic cages for collection of 24h urine samples. Then, animals were euthanized, plasma and kidneys were harvested for assessment of renal injury. No significant differences in body weight were observed between groups. GPER1 deletion in virgin mice did not impact food intake or urinary Na+ excretion (UNaV). Former pregnancies reduced food intake (p=0.0003) and UNaV (p&lt;0.0001) in GPER1 KO mice. To assess renal function, we measured urinary albumin excretion and plasma creatinine (Cr). GPER1 deletion increased urinary albumin excretion in virgin mice (KO: 16.47±2.08; WT: 6.06±1.04 μg/day; n=6 &amp; 7 respectively; p=0.0005). Interestingly, prior pregnancies eliminated this genotypic difference in albuminuria (KO: 6.12±1.44; WT: 5.79±1.66 μg/day; n=6 &amp; 8 respectively; p=0.986). GPER1 deletion also resulted in higher plasma Cr level in virgin mice (KO: 1.36±0.08; WT: 0.97±0.05 mg/mL; n=6 &amp; 7 respectively; p=0.0018). Prior pregnancies decreased plasma Cr levels in GPER1 KO mice (0.84±0.10 mg/dL, n= 5; p= 0.0012). We also measured urinary excretion of endothelin (ET‐1) and aldosterone which are causally linked to renal injury. GPER1 KO elicited greater levels of urinary ET‐1 compared to WT virgin mice (0.37±0.06 vs.0.17±0.01 pg/day; n=6 &amp; 7, respectively; p=0.0063). Previous pregnancies lowered urinary levels of ET‐1 and aldosterone in GPER1 KO mice (ET‐1: p=0.0049; aldosterone: p=0.0099). Furthermore, histological assessment of kidney sections revealed diffuse proliferative glomerulonephritis (GN) with intracapillary hyaline/protein thrombi, in GPER1 KO virgin mice only. No significant acute tubular injury was observed in any group. Further experiments will determine blood pressure and characterize the glomerular lesions evident in aged GPER1 KO virgin mice. Overall, our data demonstrate significant glomerular injury (GN), greater plasma Cr and greater urinary levels of albumin and ET‐1 in GPER1 KO virgin mice compared to WT virgin and previously‐pregnant GPER1 KO aged mice. The current data suggest that GPER1 and former pregnancies provide protection against glomerular injury in aged females.

Diverse and atypical manifestations of Q fever in a metropolitan city hospital: Emerging role of next-generation sequencing for laboratory diagnosis of Coxiella burnetii

Although Q fever has been widely reported in the rural areas of China, there is a paucity of data on the epidemiology and clinical characteristics of this disease in large metropolitan cities. In this study, we profile the epidemiology and clinical manifestations of Q fever from a tertiary hospital in Shenzhen, a Southern Chinese metropolitan city with a large immigrant population from other parts of China. A total of 14 patients were confirmed to have Q fever during a nine-year-and-six-month period, five of whom were retrospectively diagnosed during case review or incidentally picked up because of another research project on unexplained fever without localizing features. Some patients had the typical exposure histories and clinical features, while a few other patients had rare manifestations of Q fever, including one with heart failure and diffuse intracapillary proliferative glomerulonephritis, a patient presenting with a spontaneous bacterial peritonitis-like syndrome, and another one with concomitant Q fever and brucellosis. Using a combination of clinical manifestation, inflammatory marker levels, echocardiographic findings and serological or molecular test results, nine, three and two patients were diagnosed to have acute, chronic and convalescent Q fever, respectively. Seven, five and two patients were diagnosed to have Q fever by serological test, nested real-time PCR and next-generation sequencing respectively. Diverse and atypical manifestations are associated with Q fever. The incidence of Q fever is likely to be underestimated. Next-generation sequencing is becoming an important diagnostic modality for culture-negative infections, particularly those that the physicians fail to recognize clinically, such as Q fever.

Immunotactoid glomerulopathy \u2013 an enigmatic case in the setting of nodal marginal zone lymphoma and systemic sclerosis sine scleroderma

BackgroundImmunotactoid Glomerulopathy (ITG) is an exceedingly rare type of glomerulopathy characterised by distinctive electron microscopic features. ITG has been linked to lymphoproliferative or autoimmune disorders. The clinical manifestations are diverse including nephrotic syndrome (NS), haematuria, acute kidney injury and end stage renal failure (ESRD). We present a case with a stage 3 Nodal Marginal Zone Lymphoma (NMZL) and systemic sclerosis sine scleroderma (SSSS), where the evolution of ITG was documented in 2 renal biopsies 19 months apart. To the best of our knowledge, no cases have been reported linking ITG to NMZL. Furthermore, there is only one non-peer reviewed report linking ITG to scleroderma. We discuss the implications of our findings and highlight the satisfactory management of the case.Case presentationA 79-year-old female with history of systemic sclerosis sine scleroderma and stage 3 NMZL presented with acute kidney injury and NS on a background of chronic kidney disease. Her first kidney biopsy showed a diffuse proliferative glomerulonephritis and her serum protein electrophoresis showed no abnormalities. She was managed satisfactorily with conservative measures. She returned 19 months later with features of fluid overload, increasing proteinuria and rising serum creatinine. A repeat serum protein electrophoresis showed excess free kappa light chains and ITG was detected in the repeat kidney biopsy. Her kidney function and proteinuria showed a good and sustained response to rituximab administered after the second biopsy.ConclusionITG is a rare type of glomerulopathy, associated with underlying haematological malignancies and autoimmune disorders that may result in ESRD.Rituximab is one of the effective agents used in the management of ITG with haematological malignancies.

Warfarin-Related Nephropathy Manifested as Diffuse Mesangial Proliferative Glomerulonephritis

Warfarin is associated with anticoagulant-related nephropathy (ARN), one of the potential side effects. This is evidenced by a progressively increasing number of detected cases of deterioration in the kidney function even in patients with normal baseline function (GFR {glomerular filtration rate}) in addition to the chronic kidney disease (CKD) patients who are already vulnerable to ARN. There has been a clinical correlation in a rapid decline of kidney function and international normalized ratio (INR) levels of greater than three. ARN is a significant but underdiagnosed complication of anticoagulation that is associated with increased renal morbidity and all-cause mortality. We want to emphasize the importance of monitoring kidney function regularly and adjusting the appropriate doses of warfarin. We present a case of a 57-year-old female who was on warfarin for the mechanical aortic valve, presented with acute kidney injury and supratherapeutic INR. Her renal biopsy showed diffuse mesangial proliferative glomerulonephritis.