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Table of Contents
JOURNAL SCAN
Year : 2020  |  Volume : 3  |  Issue : 1  |  Page : 37-39

Journal scan


Division of Pediatric Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication27-Jun-2020

Correspondence Address:
Priyanka Khandelwal
Division of Pediatric Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AJPN.AJPN_13_20

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How to cite this article:
Khandelwal P. Journal scan. Asian J Pediatr Nephrol 2020;3:37-9

How to cite this URL:
Khandelwal P. Journal scan. Asian J Pediatr Nephrol [serial online] 2020 [cited 2020 Oct 20];3:37-9. Available from: https://www.ajpn-online.org/text.asp?2020/3/1/37/288149




  EULAR 2019 Guidelines for Lupus Nephritis Top


New consensus recommendations for the management of lupus nephritis (LN) were issued jointly by the European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association and published online in the Annals of the Rheumatic Diseases in March 2020. The guideline recommends the use of intravenous (IV) methylprednisolone followed by low-dose IV cyclophosphamide or mycophenolate mofetil (MMF) as the standard induction agents (Grade A), including for Class V LN (Grade B). The combination of MMF (1–2 g/day) with tacrolimus is recommended as an alternative induction strategy, especially in patients with nephrotic range proteinuria (Grade B). High-dose IV cyclophosphamide may be considered for severe/crescentic LN (Grade B) and tacrolimus monotherapy for pure lupus Class V (Grade B). MMF or azathioprine is equally favored as maintenance agents (Grade A). Steroids are advised to be tapered to ≤7.5 mg/day by 3–6 months with consideration of withdrawal (steroids followed by immunosuppressive drugs) after 3–5 years of complete clinical response (Grade C). Revised recommendations on treatment targets include: preservation of renal function and reduction in proteinuria of at least 25% by 3 months (Grade D), 50% by 6 months (Grade B), and urine protein-to-creatinine ratio below 0.5–0.7 by 12 months (Grade B); this might be assessed later in patients with baseline nephrotic range proteinuria. Evidence is limited for refractory disease, defined as failure to meet the above treatment goals; switch of induction agents or rituximab may be considered (Grade C). The guidelines assign Grade C recommendation for belimumab as a steroid-sparing agent, especially for extrarenal lupus. The current recommendation also includes statements for end-stage renal disease and transplantation with immunosuppression guided by transplant protocols and/or extrarenal manifestations.

Fanouriakis A, Kostopoulou M, Cheema K, Anders HJ, Aringer M, et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA–EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis 2020;doi: 10.1136/annrheumdis-2020-216924.


  Plasma Exchange for Antineutrophil Cytoplasmic Antibody Vasculitis (PEXIVAS): Is Evidence Still Insufficient? Top


Plasma exchange (PEX) and immunosuppression have been the cornerstone of the management of severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Utility of PEX in addition to immunosuppression alone was demonstrated by the landmark MEPEX trial that showed 50% relative reduction in the need for renal replacement therapy at 1 year. In 2011, Walsh et al. performed a meta-analysis of nine studies to conclude that PEX was beneficial for renal survival, but there was no evidence that it decreased mortality. The authors determined that adequate power would require 1487 patients and that an additional randomized controlled trial (RCT) with 500 patients could potentially allow a confident conclusion to be drawn. The authors therefore planned and conducted the open-label PEXIVAS trial, recruiting 704 patients across 16 countries in the largest RCT ever performed in severe AAV; the results of this study were published in the February 2020 issue of New England Journal of Medicine.

In this trial, Walsh et al. used a 2 × 2 factorial design to compare standard versus reduced dose (60% lower at 6 months) glucocorticoid regimens with or without adjuvant PEX, in patients >15 years of age with renal injury (estimated glomerular filtration rate <50 ml/min/1.73 m 2) or pulmonary hemorrhage. Primary outcome was all-cause mortality or progression to end-stage kidney disease over follow-up of median 2.9 years. The authors showed that PEX did not improve renal survival or mortality and that low-dose steroids were not inferior to standard dose and were associated with reduced risk of serious infections. The chief criticism of the trial was the absence of histologic assessment of chronicity at the outset without which the benefit of PEX in those with minimal renal scarring cannot be definitively ascertained. Moreover, certain estimates such as diffuse alveolar hemorrhage had large confidence intervals in the subgroup analyses; the benefit of PEX on mortality due to pulmonary hemorrhage was not assessed. Therefore, until evidence from subsequent meta-analyses emerges, perhaps PEX will continue to be used in carefully selected subgroups with histologically active disease or pulmonary hemorrhage, while the reduced dose oral glucocorticoids can be adopted safely.

Walsh M, Merkel PA, Peh CA, Szpirt WM, Puéchal X, Fujimoto S, et al. PEXIVAS Investigators. Plasma exchange and glucocorticoids in severe ANCA-associated vasculitis. N Engl J Med 2020;382:622-31.


  Prescribing Peritoneal Dialysis: Key Recommendations of the International Society for Peritoneal Dialysis Top


The International Society for Peritoneal Dialysis (PD) has recently updated the evidence-based guidelines on the prescription of PD. The emphasis of these guidelines, published online in January 2020 in Pediatric Dialysis International, is to set realistic goals that maintain quality of life by shared decision-making between patient and team providing PD. The guidelines recommend regular assessments and optimization of volume status, blood pressure, and nutritional status, as well as determination and preservation of residual renal function (RRF). The authors do not recommend a specific target of small solute clearance if symptoms, nutrition, and volume status are controlled, as there is no evidence that increasing Kt/V >1.7 may improve mortality. While various modalities of PD seem to be similar in the preservation of RRF, volume depletion and hypotension are shown to adversely affect RRF. There is strong evidence to suggest improvement in urine output following use of neutral pH and low glucose degradation product dialysate for the first 12–24 months after starting PD; these are recommended to preserve RRF. Once-daily icodextrin should be considered in patients failing to maintain euvolemia due to insufficient peritoneal ultrafiltration. Incremental dialysis is an attractive option, especially for resource-constrained settings, with comparable outcomes to standard prescription. The guidelines also list the clinical and biochemical characteristics that point toward stepping up the PD prescription. Practice points for resource-constrained, low-middle income countries are also provided.

Brown EA, Blake PG, Boudville N, Davies S, de Arteaga J, Dong J, et al. International Society for Peritoneal Dialysis practice recommendations: Prescribing high-quality goal-directed peritoneal dialysis. Perit Dial Int 2020; 40: 244-253


  A New Gene for Distal Renal Tubular Acidosis Top


Primary distal renal tubular acidosis (RTA), characterized by impaired distal urinary acidification, is chiefly due to genetic defects in the vacuolar H +-ATPases (V-type ATPase) pump located in the alpha-intercalated cells in the late distal tubule and collecting duct. While genetic defects in ATP6V0A4, ATP6V1B1, and SLC4A1 comprise 60%–80% of patients, FOXI1 and WDR72 that encode subunits or regulate trafficking of the V-type ATPase have recently been identified as additional causes. In the March issue of Kidney International, Jobst-Schwan et al. report ATP6V1C2, a gene encoding another subunit of the V-type ATPase pump, as a candidate for distal RTA. Patients with familial distal RTA subjected to panel sequencing and/or whole-exome sequencing identified variants in 12 of 17 families in previously reported genes (including WDR72). Homozygosity mapping in the remaining unsolved families detected a variant in ATPV1C2 in a single patient that changed isoleucine at position 168 into threonine; in silico modeling predicted significant conformational changes in the protein. Authors performed extensive in vivo downstream investigations to corroborate its pathogenicity by introducing the mutation in yeast, the growth of which depends on the V-type ATPase pump. Impaired growth of the mutant yeast, lack of ATPase activity in the vacuolar vesicles, and altered stability of the V1 subunit of the pump strongly support its deleteriousness by affecting V-type ATPase pump. The authors describe two patients with distal RTA associated with dental enamel defects (amelogenesis imperfecta) due to novel WDR72 mutations and expand the phenotype of this poorly characterized subset of patients. The study highlights the power of genetic discovery to enable an understanding the molecular mechanism of tubular diseases.

Jobst-Schwan T, Klämbt V, Tarsio M, Heneghan JF, Majmundar AJ, Shril S, et al. Whole exome sequencing identified ATP6V1C2 as a novel candidate gene for recessive distal renal tubular acidosis. Kidney Int 2020;97:567-79.


  Unraveling Human Leukocyte Antigen Signatures: A “complement” to the Pathogenesis of Membranoproliferative Glomerulonephritis Top


Membranoproliferative glomerulonephritis (MPGN) is a rare, complex, and severe disease with high rates of progression to end-stage renal disease and recurrence following transplantation. Dysregulation of the complement system is shown to be a major risk factor for the development of MPGN; familial and nonfamilial cases have been shown to harbor mutations in genes regulating the complement pathway. In a large genome-wide association study from Europe, Levine et al. have attempted to characterize the genetic factors in MPGN. The results, published in the February 2020 issue of Journal of the American Society of Nephrology, may lead to a paradigm shift in understanding the pathogenesis of MPGN. Whole-genome data from 165 cases of primary MPGN and 6442 unrelated European controls revealed no enrichment of rare variants in genes regulating the alternative complement pathway (6.8% in cases versus 5.9% in controls). This study had >92% power to detect a >15% increase in the burden of rare complement gene variants. No difference in genetic profiles was observed in patients with immune-complex, C3 glomerulonephritis, and dense deposit disease, as well as those with and without C3 nephritic factor (C3NeF). A common variant locus was identified at the human leukocyte antigen (HLA) locus 6p21.32, mapping to the haplotypes DQA1*05:01, DQB1*02:01, and DRB1*03:01. These findings were replicated on the analysis of HLA serotypes in an independent cohort of 338 patients with MPGN and 15,614 with unrelated renal failure. The strong association of HLA locus with MPGN has led the authors to hypothesize that the pathogenicity of MPGN is primarily driven by autoimmunity rather than an underlying monogenic disorder in complement regulation. The prevalence of autoantibodies such as C3Nef and antibodies to factor H, factor B, and C3b in patient with MPGN supports this hypothesis.

Levine AP, Chan MMY, Sadeghi-Alavijeh O, Wong EKS, Cook HT, Ashford S, et al. Large-scale whole-genome sequencing reveals the genetic architecture of primary membranoproliferative GN and C3 glomerulopathy. J Am Soc Nephrol 2020;31:365-73.

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Conflicts of interest

There are no conflicts of interest.






 

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