Association of Obesity With Kidney and Cardiac Outcomes Among Patients With Glomerular Disease: Findings From the Cure Glomerulonephropathy Network.

RATIONALE & OBJECTIVE: The influence of obesity on cardiorenal outcomes in individuals with glomerular disease is incompletely known. This study examined the association between obesity and kidney and cardiovascular outcomes in children and adults with glomerular kidney disease. STUDY DESIGN: Prospective, multicenter, observational study. SETTING & PARTICIPANTS: Participants in the Cure Glomerulonephropathy Network (CureGN) who were≥5 years of age at enrollment. EXPOSURE: Adult body mass index (BMI) groups: 20-24 (healthy) versus 25-34 (overweight/class 1 obesity) versus≥35 (class 2-3 obesity); and pediatric BMI percentiles: 5th-84th (healthy) versus 85th-94th (overweight) versus≥95th (obese). OUTCOME: A composite kidney outcome (40% estimated glomerular filtration rate [eGFR] decline or kidney failure) and a composite cardiovascular outcome (myocardial infarction, stroke, heart failure, or death). ANALYTICAL APPROACH: Time to composite primary outcomes by BMI strata were estimated using Kaplan-Meier analysis. The adjusted associations between BMI and outcomes were estimated using Cox proportional hazards analysis. RESULTS: The study included 2,301 participants (1,548 adults and 753 children). The incidence of the primary kidney end point was 90.8 per 1,000 person-years in adults with class 2-3 obesity, compared with 58.0 in normal weight comparators. In the univariable analysis, class 2-3 obesity was associated with the primary kidney outcome only in adults (HR, 1.6 [95% CI, 1.1-2.2], P=0.006) compared with the healthy weight groups. In the multivariable adjusted analysis, class 2-3 obesity did not remain significant among adults when controlling for baseline eGFR and proteinuria. Adults with class 2-3 obesity had an incidence of 19.7 cardiovascular events per 1,000 person-years and greater cardiovascular risk (HR, 3.9 [95% CI, 1.4-10.7], P=0.009) in the fully adjusted model. LIMITATIONS: BMI is an imperfect indicator of adiposity. Residual confounding may exist from socioeconomic factors. CONCLUSIONS: Among adult patients in CureGN, class 2-3 obesity is associated with cardiovascular but not kidney outcomes when adjusted for potential confounding factors. PLAIN-LANGUAGE SUMMARY: Obesity is a risk factor for adverse heart and kidney outcomes in patients with chronic kidney disease, but whether it is associated with these outcomes in patients with glomerulonephropathy is not known. This study used existing data from a large sample of adults and children with glomerular diseases to address this question. The findings suggest that obesity increases the risk of cardiovascular but not kidney disease events in adult patients with glomerular disease.

Sodium-glucose cotransporter 2 inhibition in primary and secondary glomerulonephritis.

BACKGROUND: The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the management glomerular/systemic autoimmune diseases with proteinuria in real-world clinical settings is unclear. METHODS: This is a retrospective, observational, international cohort study. Adult patients with biopsy-proven glomerular diseases were included. The main outcome was the percentage reduction in 24-h proteinuria from SGLT2i initiation to 3, 6, 9 and 12 months. Secondary outcomes included percentage change in estimated glomerular filtration rate (eGFR), proteinuria reduction by type of disease and reduction of proteinuria ≥30% from SGLT2i initiation. RESULTS: Four-hundred and ninety-three patients with a median age of 55 years and background therapy with renin-angiotensin system blockers were included. Proteinuria from baseline changed by -35%, -41%, -45% and -48% at 3, 6, 9 and 12 months after SGLT2i initiation, while eGFR changed by -6%, -3%, -8% and -10.5% at 3, 6, 9 and 12 months, respectively. Results were similar irrespective of the underlying disease. A correlation was found between body mass index (BMI) and percentage proteinuria reduction at last follow-up. By mixed-effects logistic regression model, serum albumin at SGLT2i initiation emerged as a predictor of ≥30% proteinuria reduction (odds ratio for albumin <3.5 g/dL, 0.53; 95% CI 0.30-0.91; P = .02). A slower eGFR decline was observed in patients achieving a ≥30% proteinuria reduction: -3.7 versus -5.3 mL/min/1.73 m2/year (P = .001). The overall tolerance to SGLT2i was good. CONCLUSIONS: The use of SGLT2i was associated with a significant reduction of proteinuria. This percentage change is greater in patients with higher BMI. Higher serum albumin at SGLT2i onset is associated with higher probability of achieving a ≥30% proteinuria reduction.

Incidence and outcomes of kidney replacement therapy for end-stage kidney disease due to primary glomerular disease in Europe: findings from the ERA Registry.

BACKGROUND: Primary glomerular disease (PGD) is a major cause of end-stage kidney disease (ESKD) leading to kidney replacement therapy (KRT). We aimed to describe incidence (trends) in individuals starting KRT for ESKD due to PGD and to examine their survival and causes of death. METHODS: We used data from the European Renal Association (ERA) Registry on 69 854 patients who started KRT for ESKD due to PGD between 2000 and 2019. ERA primary renal disease codes were used to define six PGD subgroups. We examined age and sex standardized incidence, trend of the incidence and survival. RESULTS: The standardized incidence of KRT for ESKD due to PGD was 16.6 per million population (pmp), ranging from 8.6 pmp in Serbia to 20.0 pmp in France. Immunoglobulin A nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) had the highest incidences, of 4.6 pmp and 2.6 pmp, respectively. Histologically non-examined PGDs represented over 50% of cases in Serbia, Bosnia and Herzegovina, and Romania and were also common in Greece, Estonia, Belgium and Sweden. The incidence declined from 18.6 pmp in 2000 to 14.5 pmp in 2013, after which it stabilized. All PGD subgroups had 5-year survival probabilities above 50%, with crescentic glomerulonephritis having the highest risk of death [adjusted hazard ratio 1.8 (95% confidence interval 1.6-1.9)] compared with IgAN. Cardiovascular disease was the most common cause of death (33.9%). CONCLUSION: The incidence of KRT for ESKD due to PGD showed large differences between countries and was highest and increasing for IgAN and FSGS. Lack of kidney biopsy facilities in some countries may have affected accurate assignment of the cause of ESKD. The recognition of the incidence and outcomes of KRT among different PGD subgroups may contribute to a more individualized patient care approach.

Acute glomerulonephritis with concurrent suspected bacterial pneumonia - is it the tip of the iceberg?

BACKGROUND: Post infectious glomerulonephritis is the most common glomerulopathy in children, occurring several weeks after nephritogenic streptococcal throat or skin infection. Reports of acute glomerulonephritis (AGN) occurring during active bacterial pneumonia in children are rare. The aim of this study was to evaluate the incidence of AGN concurrent with bacterial pneumonia in children. METHODS: We reviewed records of all children admitted with a diagnosis of pneumonia to the pediatric department in a single tertiary medical center between January 2015 and April 2023. Patients with bacterial pneumonia and concurrent glomerulonephritis were included. RESULTS: Eleven (0.98%) of 1,123 patients with bacterial pneumonia had concurrent AGN. All were males with a median age of 2.7 years (range 1-13). Mean time from bacterial pneumonia onset to acute glomerulonephritis symptoms was 2.7 ± 1.5 days. Five (45%) patients had evidence of pneumococcal infection. Hypertension was found in 10 (91%) patients. Mean trough eGFR was 43.5 ± 21.4 ml/min/1.73 m2 (range 11-73). Ten patients (91%) had low C3 levels. Median urinary protein-to-creatinine ratio was 2.5 mg/mg (IQR 2.15-14.75). All patients fully recovered. Microscopic hematuria was the last finding to normalize after a median of 29.5 days (IQR 17.25-38). CONCLUSION: AGN during bacterial pneumonia may be more frequent than previously recognized. Kidney prognosis was excellent in all patients. Prospective studies are needed to evaluate the impact of this condition.

An unusual etiology in an 8-year-old girl with chest pain and elevated troponin-I.

Acute post-streptococcal glomerulonephritis (APSGN) is the most common glomerulonephritis of childhood, and clinical presentation can vary widely. This case report presents an atypical manifestation of APSGN in an 8-year-old female patient with pleuritic chest pain and elevated troponin-I, despite lacking classical kidney symptoms. Imaging studies showed cardiomegaly and interstitial lung opacities. Further investigations revealed hematuria and proteinuria, and the diagnosis was confirmed through elevated antistreptolysin-O (ASO) titers and low complement 3 (C3) levels. The patient was successfully managed with fluid restriction, diuretics, and antihypertensives, resulting in the resolution of symptoms and normalization of laboratory values. This case highlights the significance of recognizing atypical manifestations of APSGN for ensuring prompt diagnosis and proper management in the pediatric population.

ANCA-associated kidney disease preceded by orbital pseudotumor.

INTRODUCTION: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and IgG4-related disease (IgG4-RD) are distinct immune disorders with overlapping clinical and laboratory features. While ANCA positivity excludes IgG4-RD in the 2019 ACR/EULAR classification, this criterion is not uniformly applied, and AAV can form inflammatory masses in various organs and show increase in IgG4 + plasma cells, similar to IgG4-RD. CASE DIAGNOSIS/TREATMENT: A 5-year-old female with history of orbital mass diagnosed as IgG4-RD presents with acute kidney injury. She has a myeloperoxidase ANCA, and kidney biopsy shows pauci-immune crescentic glomerulonephritis and acute tubulointerstitial nephritis with increased IgG4 + plasma cells and tubular basement membrane (TBM) deposits. CONCLUSION: In isolation, TBM deposits and increased IgG4 + plasma cells are suggestive of IgG4-RD. In the context of a positive ANCA and pauci-immune crescentic glomerulonephritis, however, increased IgG4 + plasma cells due to AAV are favored. In cases with features of IgG4-RD, ANCA positivity suggests an alternate diagnosis of AAV to be more likely.

Fibrillary glomerulonephritis in a patient with rheumatoid arthritis: A case report and review of the literature.

Fibrillary glomerulonephritis (FGN) is a rare glomerular disease defined by the presence of microfibrils that deposit within the glomeruli. While initially thought to be idiopathic, FGN is now recognized to be associated with infection, malignancies, and autoimmune disorders. We describe a case of biopsy-proven FGN in a patient with seropositive rheumatoid arthritis (RA) and provide a review of the literature regarding the association of FGN with RA.

Diagnosis of membranous nephropathy with Anti-GBM glomerulonephritis: a case series report.

BACKGROUND: The concomitant occurrence of membranous nephropathy and anti-glomerular basement (anti-GBM) disease has been previously described but is extremely rare. However, delayed recognition or misdiagnosis leads to delayed treatment, resulting in worse renal and patient outcomes. CASE PRESENTATION: We present 3 patients with rapidly progressive glomerulonephritis (RPGN), anti-GBM and serum-positive M-type phospholipase A2 receptor (anti-PLA2R) antibody. Renal biopsies revealed PLA2R-associated membranous nephropathy with anti-GBM glomerulonephritis. We analyzed the clinical and pathological characteristics and discussed that the correct diagnosis of membranous nephropathy with anti-GBM should rely on a combination of renal biopsy findings and serological testing. Despite aggressive treatment, one patient received maintenance hemodialysis, one patient progressed to CKD 3 stage, and the other patient died of cerebral infarction. CONCLUSION: The simultaneous occurrence of membranous nephropathy and anti-GBM disease is extremely rare. The correct diagnosis of membranous nephropathy with anti-GBM relies on a combination of renal biopsy findings and serological testing. Early diagnosis is needed to improve the renal dysfunction.

Pediatric IgA-Dominant Infection-Related Glomerulonephritis.

The concept of infection-related glomerulonephritis (IRGN) has been introduced as adults diagnosed with glomerulonephritis often have coexisting active infections. Furthermore, IgA-dominant IRGN is associated with staphylococcal infections in adults with comorbidities, which often progress to end-stage renal disease. Little is known about IgA-dominant IRGN in children, and no consensus for a management strategy of this condition has been reached. We describe the case of a 9-year-old boy with IgA-dominant IRGN that was diagnosed using specific staining for nephritis-associated plasmin receptor (NAPlr)/plasmin activity and galactose-deficient IgA1 (Gd-IgA1), a marker of IgA nephropathy. The patient was successfully treated using a combination of prednisolone, mizoribine (an immunosuppressive drug), and lisinopril (an angiotensin-converting enzyme inhibitor) and three courses of methylprednisolone pulse therapy. The patient was admitted to our hospital with generalized edema, gross hematuria, proteinuria, hypertension, and renal dysfunction. Hypocomplementemia contributed to a diagnosis of IRGN, although the causative organism was unknown. A renal biopsy performed when the patient presented with nephrotic syndrome showed IgA deposition, positive staining for NAPlr, and negative staining for Gd-IgA1, in addition to findings consistent with IRGN, leading to a pathologic diagnosis of IgA-dominant IRGN. The histological staining for NAPlr/plasmin activity and Gd-IgA1, together with clinical symptoms, could be helpful for diagnosing IgA-dominant IRGN. Our findings indicate that otherwise healthy children can also develop IgA-dominant IRGN. Therefore, early diagnosis and aggressive treatment should be considered when IgA-dominant IRGN is suspected to avoid the possibility of incomplete recovery of renal function.

Similar incidence of graft glomerulonephritis in recipients with definitively diagnosed glomerulonephritis and those with unknown etiology: a retrospective observational study.

OBJECTIVE: In China, most of the patients who underwent kidney transplants have unknown causes of end-stage renal disease (uESRD). However, little is known regarding the incidence of graft glomerulonephritis (GN) and graft survival in kidney transplant recipients (KTRs) with uESRD. METHODS: In this retrospective cohort study, 473 of the 565 KTRs who underwent kidney transplantation (KTx) from 2015 to 2020 were included. We mainly observed the occurrence of graft GN between uESRD group and definitively diagnosed GN group, and repeatedly compared after propensity score matching (PSM). RESULTS: The median follow-up was 50 months in 473 KTRs, and about 75% of KTRs of native kidney disease of unknown etiology. The total cumulative incidence of graft GN was 17%, and no difference was observed between the definitively diagnosed GN group and the uESRD group (p = 0.76). Further, PSM analysis also showed no difference in the incidence of graft GN between the 2 groups. Multivariable analysis disclosed males (p = 0.001), younger age (p = 0.03), and anti-endothelial cell anti-body (AECA) positive pre-KTx (p = 0.001) were independent risk factors for graft GN. CONCLUSIONS: The incidence of graft GN was similar between uESRD and definitively diagnosed GN group. The allograft survival was also similar between two groups.

Group A Streptococcus Infections.

Group A Streptococcus causes a variety of clinical manifestations, including pharyngitis and skin and soft tissue infections as well as more invasive disease. There are also multiple nonsuppurative complications of group A Streptococcus infection, including acute rheumatic fever and poststreptococcal glomerulonephritis. Pediatricians should be able to diagnose and treat the various presentations of the infection.

Clinicopathologic Study of Sickle Cell-associated Kidney Disease: A Nigerian Experience.

BACKGROUND: Improvements in sickle cell disease (SCD) care have resulted in the survival of many patients into adulthood, although this is accompanied by the increased incidence of end-organ damage, including chronic kidney disease (CKD). OBJECTIVES: This study assessed the prevalence, pattern and predictors of renal dysfunction in SCD patients and investigated the associated renal histopathologic changes. METHODS: We evaluated 105 patients with SCD, for proteinuria, estimated glomerular filtration rate (eGFR), and tubular dysfunction. Renal biopsy was conducted on 22 patients who qualified. Data were analysed using SPSS package version 23. RESULTS: Thirty-seven (35.2%) of the 105 patients had CKD, as defined by an eGFR of 60 ml/min/1.73 m2 and/or proteinuria. The fractional excretion of potassium (FEK) was elevated in all patients, whereas the fractional excretion of sodium (FENa) was elevated in 98.1%. Glomerular filtration rate was negatively correlated with irreversible percentage sickle cell count (r = -0.616, P = 0.0001), FEK (r = -0.448, P = 0.0001) and FENa (r = -0.336, P = 0.004). Age, irreversible percentage sickle cell count, haemoglobin levels and FENa were the major predictors of CKD. The histological pattern in the 22 patients who had biopsies was consistent with mesangioproliferative glomerulonephritis 11 (50%), minimal change disease 6 (27.3%), focal segmental glomerulosclerosis 3 (13.6%) and interstitial nephritis 2 (9.1%). CONCLUSIONS: CKD was prevalent in SCD patients, and it was characterised by tubular dysfunction and mesangioproliferative glomerulonephritis. The main predictors of CKD were increased age, severity of vaso-occlusive crisis, worsening anaemia and tubular dysfunction.

[Comparison of thrombodynamic methods and routine hemostasis tests in the evaluation of hypercoagulable syndrome in chronic glomerulonephritis].

BACKGROUND: Nephrotic syndrome (NS) is associated with a high risk of thrombotic complications. In this group of patients, routine local tests for assessing hemostasis do not accurately reflect hypercoagulable state. Global functional tests for assessing hemostasis, including thrombodynamics (TD), are considered promising for assessing disorders in the blood coagulation system of these patients. AIM: To compare the rate of hypercoagulability according to routine hemostatic tests and TD and to evaluate the factors associated with increased risk of thrombotic complications in patients with chronic glomerulonephritis (CGN). MATERIALS AND METHODS: The study included 94 patients with active CGN who were not receiving anticoagulant therapy; 63 (80.3%) patients had NS, and 31 (19.7%) had active CGN without NS. Hemostasis parameters were assessed using local coagulation tests and TD test. Using logistic regression analysis, factors associated with the risk of thrombosis were assessed. RESULTS: Of the 94 patients with active CGN in 63 without preventive anticoagulant therapy, hypercoagulability according to routine tests was detected in 6 (9.5%) patients with NS and in 3 (9.7%) patients without NS (p<0.05). Hypercoagulability according to the TD test was detected in 24 (53.9%) patients with NS and in 5 (32.2%) without NS (p<0.05). The formation of spontaneous clots was observed in 29 (30.9%) of patients with CGN, most of them 24 (83%) with NS. 10.6% of patients in our cohort experienced thromboembolic events. The risk of thromboembolic events according to the univariate regression analysis was associated with older age, higher lipid levels, use of glucocorticosteroids and detection of spontaneous clots by the TD test. No association of thromboembolic events with abnormalities in routine hemostasis tests was obtained. CONCLUSION: In patients with CGN with nephrotic syndrome, hypercoagulability is detected in 9.5% of cases with routine coagulation tests and in 53.9% of cases with TD test. Detection of spontaneous clots by TD test is associated with a risk of thromboembolic events.

[Anemia of chronic diseases in the early stages of chronic kidney disease as a risk factor for cardiovascular complications in patients with glomerulonephritis].

AIM: To determine biomarkers of anemia of chronic disease (ACD) in patients with glomerulonephritis (GN) in the early stages of CKD, to assess their role as risk factors for cardiovascular complications (CVС). MATERIALS AND METHODS: Seventy nine patients with GN were studied, among them: 40 with primary сhronic GN (CGN), 39 with secondary forms:19 - GN with ANCA-associated systemic vasculitis, 20 - GN with systemic lupus erythematosus (SLE) at early (all I-II) CKD stages. In all patients, the level of serum C-reactive protein (CRP), hepcidin, interferon γ, and the circulating form of protein Klotho (s-Klotho) were determined. When a relative iron deficiency was detected [transferrin iron saturation coefficient (TSAT) <20%], patients were administered parenterally iron [III] sucrose hydroxide complex (Venofer). RESULTS: The frequency of anemia among patients with systemic diseases is 3.2 times higher than among patients with primary CGN. Patients with anemia (group I; n=43) had higher rates of daily proteinuria (p<0.001), systolic blood pressure (p<0.05), serum levels of interferon γ (p<0.001) and hepcidin (p<0.001) and lower values of eGFR (p<0.05) than patients without anemia (group II; n=36). A strong inverse correlation was noted between the level of hepcidin and the content of iron in serum (r=-0.856; p<0.001), between the level of hemoglobin and the level of interferon γ (r=-0.447; p<0.05), hepcidin (r=-0.459; p<0.05) and CRP (r=-0.453; p<0.05). A significant inverse correlation was found between the level of hemoglobin and CVC risk factors - the value of systolic blood pressure (r=-0.512; p<0.05) and the mass index of the left ventricular myocardium (r=-0.619; p<0.01). At the same time, the contribution of 2 from 6 analyzed factors, hepcidin and eGFR, to the development of ACD was 92.5%, of which 86.6% accounted for hepcidin. A strong direct correlation was also found between a decrease in hemoglobin level and a decrease in the level of s-Klotho protein (r=0.645; p<0.001), a decrease in the level of s-Klotho and an increase in the level of serum hepcidin (r=-0.541; p<0.05). The leading value of anemia (beta -0,29; p=0,04) and depression of the s-Klotho level (beta -0,44; p=0,02) as independent cardiovascular risk factors in this group of patients was confirmed by multivariate analysis. In patients with identified deficiency of iron (n=40), after 3-4 weeks of intravenous administration of venofer, the target level of hemoglobin (Нb>120 g/l) and transferrin saturation with iron (TSAT>20%) were achieved. CONCLUSION: Among the biomarkers of ACD in patients with immunoinflammatory diseases of the kidneys (primary and secondary СGN), the increase in the serum level of hepcidin is greatest importance. The concomitant to anemia decrease in s-Klotho is a leading risk factor for CVС in CKD. Early correction of ACD with iron supplements makes it possible to achieve target levels of Hb and TSAT and have subsequently a positive effect on the production of s-Klotho and the severity of left ventricular hypertrophia.

The complement system in antineutrophil cytoplasmic antibody-associated vasculitis: pathogenic player and therapeutic target.

PURPOSE OF REVIEW: The purpose of this review is to discuss the role of the complement system in the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) as well as the employment of complement inhibitors in AAV treatment. RECENT FINDINGS: AAV has traditionally been considered a pauci-immune disease until recent findings demonstrated the pathogenic role of the complement system. The complement alternative pathway is crucial in AAV, and C5a seems to be a key molecule for AAV to develop. Avacopan, a C5a-receptor (C5aR) antagonist, proved effective in achieving AAV remission and ameliorating kidney function. SUMMARY: The increased circulating levels of some complement components - as well as the consumption of others - in patients with AAV suggested a systemic activation of the complement system. Low C3 levels correlate with a more aggressive disease and a worse renal prognosis. In ANCA-associated glomerulonephritis, renal deposits of C3d and properdin, suggestive of local alternative pathway activation, correlate with glomerular crescents and proteinuria. The interaction between C5a and neutrophil triggers alternative pathway activation, suggesting the central role of C5a in AAV pathogenesis. Avacopan, a C5aR inhibitor, showed beneficial effects in AAV and represents a promising therapy to achieve sustained remission and to spare glucocorticoids.

Recurrence of immune complex and complement-mediated membranoproliferative glomerulonephritis in kidney transplantation.

INTRODUCTION: Membranoproliferative glomerulonephritis (MPGN) represents a histologic pattern of glomerular injury that may be due to several aetiologies. Few studies have comprehensively analysed the recurrence of MPGN according to the current classification system. METHODS: We collected a multicentre, retrospective cohort of 220 kidney graft recipients with biopsy-proven native kidney disease due to MPGN between 1981 and 2021 in 11 hospitals. Demographic, clinical and histologic parameters of prognostic interest were collected. The main outcomes were time to kidney failure, time to recurrence of MPGN and disease remission after recurrence. RESULTS: The study group included 34 complement-mediated and 186 immune complex-mediated MPGN. A total of 81 patients (37%) reached kidney failure in a median follow-up of 79 months. The main predictors of this event were the development of rejection episodes and disease recurrence. In all, 54 patients (25%) had a disease recurrence in a median of 16 months after kidney transplantation. The incidence of recurrence was higher in patients with dysproteinaemia (67%) and complement-mediated MPGN (62%). In the multivariable model, complement-mediated MPGN emerged as a predictor of recurrence. A total of 33 patients reached kidney failure after recurrence. The main determinants of no remission were early time to recurrence (<15 months), estimated glomerular filtration rate <30 mL/min/1.73 m2 and serum albumin <3.5 g/dL at the time of recurrence. CONCLUSIONS: One-fourth of the patients with native kidney disease due to MPGN developed clinical recurrence in the allograft, especially in cases with complement-mediated disease or in those associated with dysproteinaemia. The kidney outcomes of disease recurrence with currently available therapies are heterogeneous and thus more effective and individualized therapies are needed.

Living Donor Kidney Transplant in Recipients With Glomerulonephritis: Donor Recipient Biologic Relationship and Allograft Outcomes.

Using the Scientific Registry of Transplant Recipients, we examined the association between donor-recipient biologic relationship and long-term recipient and allograft survival among glomerulonephritis (GN) patients. Four GN types were studied: membranous nephropathy, IgA, lupus-associated nephritis, and focal segmental glomerulosclerosis (FSGS). We identified all adult primary living-donor recipients between 2000 and 2018 (n = 19,668): related (n = 10,437); unrelated (n = 9,231). Kaplan-Meier curves were generated for the recipient, death-censored graft survival and death with functioning graft through ten years post-transplant. Multivariable Cox proportional hazard models were used to examine the association between the donor-recipient relationship and outcomes of interest. There was an increased risk for acute rejection by 12 months post-transplant among the unrelated compared to the related group in IgA (10.1% vs. 6.5%, p<0.001), FSGS (12.1% vs. 10%, p-0.016), and lupus nephritis (11.8% vs. 9.2%; p-0.049). The biological donor-recipient relationship was not associated with a worse recipient or graft survival or death with functioning graft in the multivariable models. These findings are consistent with the known benefits of living-related-donor kidney transplants and counter the reports of the potential adverse impact of the donor-recipient biologic relationship on allograft outcomes.

Utilizing therapeutic drug monitoring to optimize therapy with eculizumab and mycophenolate mofetil in a child with C3 glomerulonephritis.

BACKGROUND: C3 glomerulonephritis (C3GN) can be a devastating disease with poor response to immunosuppressive therapy. Complement inhibition with eculizumab has had equivocal results in patients with C3GN. CASE-DIAGNOSIS/TREATMENT: We report a case of a 6-year-old boy with C3GN presenting with nephrotic syndrome, severe hypertension and impaired kidney function. He did not respond to initial treatment with prednisone and mycophenolate (mofetil and sodium), and subsequent treatment with standard dosing of eculizumab. Pharmacokinetic studies identified a lack of eculizumab exposure and subsequent intensification of treatment with weekly dosing of eculizumab led to significant clinical improvement: his kidney function normalized, hypertension (weaned off 3 antihypertensive drugs), edema and proteinuria improved. Additionally, exposure to mycophenolic acid (MPA), active metabolite of mycophenolate, determined by area under the concentration-time curve of MPA was low throughout, despite significant dosing escalation. CONCLUSIONS: This case report demonstrates that individualized therapy guided by therapeutic drug monitoring might be needed in patients with nephrotic range proteinuria treated with eculizumab and mycophenolate (mofetil and sodium), an important finding that needs to be considered for further treatment trials.

How to define and assess the clinically significant causes of hematuria in childhood.

Given the wide diversity of causes of hematuria, ranging from simple urinary tract infections with rapid recovery to severe glomerulonephritis with fast decline in kidney function, it is essential to recognize the underlying disease. The first objective of the assessment is to determine whether the cause of the hematuria is medically significant. The combination of hematuria with proteinuria, the presence of hypertension, or worsening kidney function can represent signs of progressive kidney disease. Differentiating the various causes of hematuria is often simple and obvious based on the clinical signs and gross appearance of the urine. However, in some instances, additional non-invasive investigations, such as ultrasound imaging, urinary red cell morphology, measurement of calcium and other solutes in the urine, evaluation of kidney function, and protein excretion, are needed to elucidate the nature of the hematuria. Taking a detailed family history can help in establishing the underlying cause in cases of familial hematuria. On the other hand, the decision to perform a kidney biopsy in children with asymptomatic hematuria remains a challenging issue for clinicians. Ultimately, the frequency of diagnosis of glomerular involvement causing hematuria may depend on the threshold for performing a kidney biopsy. The following review will focus on the diagnostics of hematuria, starting with difficulties regarding its definition, followed by various means to differentiate between urinary, glomerular, and other causes, and finally reviewing the most common diseases that, due to their frequency or their effect on kidney function, present a diagnostic challenge in everyday practice.

Risk factors associated with short- and long-term kidney injury in children with post infectious glomerulonephritis.

BACKGROUND: Post infectious glomerulonephritis (PIGN) is the most common form of acute glomerulonephritis in children. The objective of this study was to evaluate the risk factors for kidney injury in children with PIGN referred to a tertiary care center. METHODS: This was a retrospective cohort study. The primary outcome was acute kidney injury (AKI) at initial presentation; secondary outcome was composite kidney injury, defined as reduced estimated glomerular filtration rate (eGFR), proteinuria, or hypertension at last follow-up. Binary logistic regression defined risk factors associated with the primary and secondary outcomes. RESULTS: We identified 125 PIGN cases with a mean age of 8.3±3.5 years at presentation and 252 ± 501 days of follow-up. Sixty-six percent (79/119) presented with AKI and 57% (71/125) were admitted to hospital. Shorter time to seeing a nephrologist (OR 6.7, 95%CI 1.8-24.6), nadir C3 < 0.12 g/L (OR 10.2, 95%CI 1.9-53.7), starting an antihypertensive medication (OR 7.6, 95%CI 1.8-31.3), and nephrotic range proteinuria (OR 3.8, 95%CI 1.2-12.4) were independent risk factors for AKI when adjusted for each other. At last follow-up 35% (44/125) of the cohort had the composite outcome, with older age at presentation (OR 1.2, 95%CI 1.04-1.4) and nadir C3 < 0.17 g/L (OR 2.6, 95%CI 1.04-6.7) being independent risk factors when adjusted for AKI. CONCLUSION: PIGN is an important cause of AKI in children and adolescents. The severity of initial illness is associated with the extent of kidney injury in both the short- and longer-term. Findings will help identify cases requiring lengthier surveillance. A higher resolution version of the Graphical abstract is available as Supplementary information.