Kidney biopsy for the diagnosis and treatment of kidney diseases. Recommendations from the French speaking Society of Nephrology (SFNDT) and French National Authority for Health (HAS) 2022

Kidney Biopsy (KB) is a crucial diagnostic tool in the field of renal diseases and is routinely performed in nephrology departments. A previous survey conducted by the Société Francophone de Néphrologie Dialyse Transplantation (SFNDT) revealed significant disparities in clinical practices, sometimes conflicting with the existing literature and recently published recommendations. In response, the SFNDT wished to promote the development of best practice guidelines, under the auspices of the French National Authority for Health (HAS), to establish a standardized framework for performing kidney biopsies in France.

La biopsie rénale (BR) est un outil diagnostique crucial dans le domaine des maladies rénales et est pratiquée en routine dans les services de néphrologie. Une précédente enquête menée par la Société francophone de néphrologie, dialyse et transplantation (SFNDT) a révélé d'importantes disparités dans les pratiques cliniques, parfois en contradiction avec la littérature existante et les recommandations récemment publiées. En réponse, la SFNDT a souhaité promouvoir l'élaboration de recommandations de bonnes pratiques, sous l'égide de la Haute Autorité de santé (HAS), afin d'établir un cadre standardisé pour la réalisation des biopsies rénales en France.

The uptake of [18F]-fluorodeoxyglucose by the renal allograft correlates with the acute Banff scores of cortex inflammation but not with the 1-year graft outcomes.

Introduction: [18F]FDG PET/CT noninvasively disproves acute kidney allograft rejection (AR) in kidney transplant recipients (KTRs) with suspected AR. However, the correlation of biopsy-based Banff vs. PET/CT-based scores of acute inflammation remains unknown, as does the prognostic performance of [18F]FDG PET/CT at one year post suspected AR. Methods: From 2012 to 2019, 114 [18F]FDG-PET/CTs were prospectively performed in 105 adult KTRs who underwent per cause transplant biopsies. Ordinal logistic regression assessed the correlation between the extent of histological inflammation and the mean standardized [18F]FDG uptake values (mSUVmean). Functional outcomes of kidney allografts were evaluated at one year post per cause biopsy and correlated to mSUVmean. Results: A significant correlation between mSUVmean and acute Banff score was found, with an adjusted R 2 of 0.25. The mSUVmean was significantly different between subgroups of "total i", with 2.30 ± 0.71 in score 3 vs. 1.68 ± 0.24 in score 0. Neither the function nor the survival of the graft at one year was statistically related to mSUVmean. Discussion: [18F]FDG-PET/CT may help noninvasively assess the severity of kidney allograft inflammation in KTRs with suspected AR, but it does not predict graft outcomes at one year.

IgG4-related membranous glomerulonephritis and generalized lymphadenopathy without pancreatitis: a case report.

BACKGROUND: IgG4-related disease is a recently described pathologic entity. This is the case of a patient with nephrotic syndrome and lymphadenopathy due to IgG4-related disease. Such a kidney involvement is quite peculiar and has only been described a few times recently. Renal biopsy showed a glomerular involvement with membranous glomerulonephritis in association with a tubulo-interstitial nephropathy. Moreover, the patient was not suffering from pancreatitis. CASE PRESENTATION: The patient is a middle-aged man of Moroccan origin. He has developed recurrent episodes of diffuse lymphadenopathies, renal failure and nephrotic syndrome. Renal biopsies showed membranous glomerulonephritis. DISCUSSION AND CONCLUSION: The diagnostic approach of this atypical presentation is discussed in this case report as well as diagnostic criteria, therapeutic strategies, biomarkers and pathophysiology of IgG4-related disease. IgG4-related membranous glomerulonephritis is a well-established cause of membranous glomerulonephritis. It must be sought after in every patient with a previous diagnosis of IgG4-related disease and in every patient with this histological finding on renal biopsy. Corticoids are still the first-line treatment of IgG4-related disease. New therapeutic strategies are needed to avoid glucocorticoids long term side-effects. Interestingly, the patient was prescribed cyclophosphamide in addition to glucocorticoids for an immune thrombocytopenia. This treatment had a very good impact on his IgG4-related disease.

In-depth phenotyping of a Donnai-Barrow patient helps clarify proximal tubule dysfunction.

BACKGROUND: The megalin/cubilin/amnionless complex is essential for albumin and low molecular weight (LMW) protein reabsorption by renal proximal tubules (PT). Mutations of the LRP2 gene encoding megalin cause autosomal recessive Donnai-Barrow/facio-oculo-acoustico-renal syndrome (DB/FOAR), which is characterized by LMW proteinuria. The pathophysiology of DB/FOAR-associated PT dysfunction remains unclear. CLINICAL CASE: A 3-year-old girl presented with growth retardation and proteinuria. Clinical examination was unremarkable, except for a still-opened anterior fontanel and myopia. Psychomotor development was delayed. At 6, she developed sensorineural hearing loss. Hypertelorism was noted when she turned 12. Blood analyses, including renal function parameters, were normal. Urine sediment was bland. Proteinuria was significant and included albumin and LMW proteins. Immunoblotting analyses detected cubilin and type 3 carbonic anhydrase (CA3) in the urine. Renal ultrasound was unremarkable. Optical examination of a renal biopsy did not disclose any tubular or glomerular abnormality. Electron microscopy revealed that PT apical endocytic apparatus was significantly less developed. Immunostaining for megalin showed a faint signal in PT cytosol contrasting with the distribution of cubilin at the apical membrane. The diagnostic procedure led to identifying two mutations of the LRP2 gene. CONCLUSIONS: The functional loss of megalin in DB/FOAR causes PT dysfunction characterized by increased urinary shedding of CA3 and cubilin.

Overlap syndrome consisting of PSC-AIH with concomitant presence of a membranous glomerulonephritis and ulcerative colitis.

The association of primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) is known as an overlap syndrome (OS). OS can also be described in the setting of concomitant presence of AIH and PSC. These diseases can in some cases be associated with ulcerative colitis. In this case report we describe, to our knowledge, the first case in the literature of a young Caucasian male suffering from ulcerative colitis and an overlap syndrome consisting of an association between PSC-AIH, with the concomitant presence of a membranous glomerulonephritis.

Two novel mutations of the CLDN16 gene cause familial hypomagnesaemia with hypercalciuria and nephrocalcinosis.

Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis is an autosomal-recessive disease caused by mutations in the CLDN16 or CLDN19 genes, which encode tight junction-associated proteins, claudin-16 and -19. The resultant tubulopathy leads to urinary loss of Mg(2+) and Ca(2+), with subsequent nephrocalcinosis and end-stage renal disease (ESRD). An 18-year-old boy presented with chronic kidney disease and proteinuria, as well as hypomagnesaemia, hypercalciuria and nephrocalcinosis. A kidney biopsy revealed tubular atrophy, interstitial fibrosis and segmental sclerosis of some glomeruli. Two novel mutations in the CLDN16 gene were identified: c.340C>T (nonsense) and c.427+5G>A (splice site). The patient reached ESRD at 23 and benefited from kidney transplantation.

Mature erythrocyte parameters as new markers of functional iron deficiency in haemodialysis: sensitivity and specificity.

BACKGROUND: The percentage of hypochromic red blood cells (RBCs) (%HYPO) has been demonstrated as the best predictor of response to iron loading in haemodialysis patients treated with recombinant human erythropoietin (rHuEPO). However, we have previously shown that this parameter is positively influenced by erythropoietic activity since reticulocytes are considered hypochromic by cell counters. New cell counters are able to determine cell volume and haemoglobin (Hb) concentration separately on reticulocytes and mature erythrocytes. The aim of this study was to assess the sensitivity and specificity of mature erythrocyte parameters in detecting functional iron deficiency (FID). METHODS: A total of 32 stable chronic haemodialysis patients in the maintenance phase of rHuEPO therapy were included. Classical parameters of iron monitoring and mature erythrocyte parameters were measured after a 4-week iron-free period. Patients were classified as responders (R) or non-responders (NR) to an iron load of 100 mg iron sucrose at each dialysis session for 4 weeks, according to whether their Hb increased by >1 g/dl at the end of iron loading. RESULTS: Twelve patients were identified as responders. Receiver operating characteristic (ROC) curve analysis demonstrated %HYPO and its corresponding parameter on mature erythrocyte, %HYPOm, as the best predictors of FID. The other parameters were ordered as follows: tranferrin saturation (TSAT), ferritin (FRT), mature RBC Hb content (CHm), mean corpuscular Hb concentration (MCHC), percentage of mature erythrocytes with a low CHm (%lowCHm), mean content in Hb (MCH) and reticulocyte Hb content CHr. Comparing the parameters at different cut-offs, the best sensitivity, specificity and efficiency were demonstrated for %HYPOm> 6%. CONCLUSION: The best efficiency to predict FID was found for %HYPOm> 6%. The predictive value of %HYPO was quite similar. The clinical impact of %HYPOm in iron monitoring should also be tested in the induction phase of rHuEPO treatment because of its independence from erythropoietic activity.

Increased iron absorption during autologous blood donation supported by recombinant human erythropoietin therapy.

BACKGROUND: Recombinant human erythropoietin (rHuEPO) therapy improves the success of autologous blood (AB) donation programs before elective surgery. The aim of this study was to evaluate iron absorption during an AB donation program with or without rHuEPO. STUDY DESIGN AND METHODS: Thirty-two patients were randomly assigned among placebo (Group 1) or 300 (Group 2) or 600 UI per kg rHuEPO (Group 3) on the first, second, and third donation visits. All patients also received daily oral iron (200 mg Fe(+)). RESULTS: The number of units collected in Group 3 was higher than in Group 1 (4.6 +/- 0.5 vs. 3.6 +/- 0.8 units; p < 0.01). Red blood cell (RBC) production increased in a rHuEPO dose-dependent manner. With rHuEPO, the RBC volume collected per unit presented a lower decrease with number of donated units than with placebo and was similar to that of homologous blood units. Storage iron did not influence the number of units collected, whereas circulating mobilizable iron was the limiting factor. Oral iron absorption increased in a rHuEPO dose-dependent manner (12-fold with 600 UI/kg rHuEPO) and was proportional to erythropoietic activity. CONCLUSION: rHuEPO does not only improve the number of AB units collected but also their quality. Storage iron cannot meet marrow iron requirements, but rHuEPO strongly increased oral iron absorption in a dose-dependent fashion through stimulation of erythropoietic activity.

Mature erythrocyte indices: new markers of iron availability.

This study was aimed at evaluating mature erythrocyte indices as new markers of iron status. Contrarily to those in the whole red blood cell (RBC) population, mature erythrocyte parameters are valid markers of iron status that remain independent of erythropoietic activity. When reticulocytosis is low, these parameters are similar to whole RBC parameters.