Progressive Kidney Failure Research Articles

Identification of Genes Associated with Familial Focal Segmental Glomerulosclerosis Through Transcriptomics and In Silico Analysis, Including RPL27, TUBB6, and PFDN5.

Focal segmental glomerulosclerosis (FSGS) is a major cause of nephrotic syndrome and often leads to progressive kidney failure. Its varying clinical presentation suggests potential genetic diversity, requiring further molecular investigation. This study aims to elucidate some of the genetic and molecular mechanisms underlying FSGS. The study focuses on the use of bioinformatic analysis of gene expression data to identify genes associated with familial FSGS. A comprehensive in silico analysis was performed using the GSE99340 data set from Gene Expression Omnibus (GEO) comparing gene expression in glomerular and tubulointerstitial tissues from FSGS patients (n = 10) and Minimal Change Disease (MCD) patients (n = 8). These findings were validated using transcriptomics data obtained using RNA sequencing from FSGS (n = 3) and control samples (n = 3) from the UAE. Further validation was conducted using qRT-PCR on an independent FFPE cohort (FSGS, n = 6; MCD, n = 7) and saliva samples (FSGS, n = 3; Control, n = 7) from the UAE. Three genes (TUBB6, RPL27, and PFDN5) showed significant differential expression (p < 0.01) when comparing FSGS and MCD with healthy controls. These genes are associated with cell junction organization and synaptic pathways of the neuron, supporting the link between FSGS and the neural system. These genes can potentially be useful as diagnostic biomarkers for FSGS and to develop new treatment options.

Slowly progressive autosomal dominant Alport Syndrome due to COL4A3 splicing variant.

Alport syndrome is a rare genetic kidney disease caused by variants in the COL4A3/A4/A5 genes. It's characterised by progressive kidney failure, though therapies targeting Renin-Angiotensin System can delay its progression. Additionally, extrarenal manifestations may sometimes coexist. Recent advances in genetic analysis and the necessity to better clarify genotype-phenotype correlations in affected patients raises the importance of detecting even cryptic splicing variants, lying in both canonical and non-canonical splice sites variants such as last exonic nucleotide variants. These variants, often, do not cause an amino acid change but alter the snRNP proteins binding. We studied a big Italian family with Alport syndrome showing a clear dominant pattern of transmission with younger family members having only haematuria and older individuals presenting with End-Stage Kidney Failure (ESKF). Kidney biopsy showed the typical disease hallmarks. We deeply mined the data for SNV and CNV through exome sequencing on DNA from both peripheral blood samples and patients' podocytes-lineage cells. We identified an already reported synonymous variant, c.765G>A (p.(Thr255Thr)), in the last exonic nucleotide of exon 13 of the COL4A3 gene. Employing the patient's podocytes we demonstrated that this variant results in exon skipping leading to an in-frame deletion of 28 amino acids without leaky effect. According to the pattern of transmission, to the kidney biopsy and to the exome data analysis we provided further evidence that autosomal dominant Alport syndrome is a well-defined clinical entity. We also confirmed the pathogenicity of the synonymous COL4A3 variant for the first time demonstrating its role in a dominant pattern of transmission.

Comparison of the Effect of Omega-3 vs. MCT Supplementation on Iron-Related Indices in Patients Undergoing Dialysis.

Chronic kidney disease (CKD), characterized by progressive kidney failure, significantly increases mortality and comorbidity risks such as anemia. This study contrasts the impacts of omega-3 and medium-chain triglycerides (MCT) oil on levels of iron, ferritin, total iron-binding capacity (TIBC), hemoglobin (Hb), and transferrin saturation in patients with CKD undergoing dialysis. This interventional trial was conducted on 120 patients with CKD undergoing dialysis in Rasht, Iran. For 8weeks, the omega-3 group was orally administered three 1000-mg capsules of omega-3 fatty acid supplement, and the MCT group was administered three 1000-mg capsules containing MCT oil daily. Serum concentrations of ferritin, iron, TIBC, Hb, and transferrin saturation were assessed pre-intervention and after the intervention. There was a significant increase in serum iron levels in the MCT group compared to the omega-3 group (103.72 ± 57.8vs. 77.48±40.13; P = 0.031). No effect was found regarding other iron-related factors such as TIBC, Hb, transferrin saturation, and ferritin levels. The results of our study indicated that taking MCT oil increased serum iron levels compared to omega-3 supplementation in patients with CKD undergoing dialysis. Further research is needed to better understand the potential benefits of MCT oils in patients with CKD.

Novel mutation in XPNPEP3 in a patient with heart failure without nephronophthisis-like nephropathy (NPHPL1): case report and literature review

Background X-prolyl aminopeptidase 3(XPNPEP3) mutations are known to cause nephronophthisis-like nephropathy-1 (NPHPL1), a rare autosomal-recessive kidney disease characterized by progressive kidney failure and cystic kidney disease in childhood. The full phenotypic spectrum associated with mutations in XPNPEP3 is not fully elucidated.Case presentationA 13-year-old Chinese female patient with intellectual disability presented with a 2-year history of convulsions and fatigue, with a recent episode of swelling, breathlessness, and nocturnal dyspnea lasting 10 days. The patient was diagnosed with heart failure and kidney failure. Whole exome sequencing revealed a homozygous c.970–2 A > G mutation in XPNPEP3 associated with severe cardiac dysfunction and neurological symptoms, including epilepsy and intellectual disability. Notably, kidney ultrasound did not reveal the typical changes of NPHPL1, and kidney failure was hypothesized to be secondary to cardiac dysfunction rather than primary kidney pathology.ConclusionsThis case suggests the possible association of additional phenotypic features associated with XPNPEP3 mutations, emphasizing the need for further investigation into the heterogeneous clinical presentations associated with XPNPEP3 mutations. The findings highlight the importance of considering alternative phenotypes in patients with genetic mutations traditionally associated with specific diseases. Segregation and functional analyses are necessary to determine causality between the c.970–2 A > G XPNPEP3 mutation and disease.

Effect of Lisinopril on Glomerular and Tubular Injury in a Surgical Rat Model of Progressive CKD and Kidney Failure

Effect of Lisinopril on Glomerular and Tubular Injury in a Surgical Rat Model of Progressive CKD and Kidney Failure

Rapidly Progressive Kidney Failure in a Patient with Longstanding Juvenile Dermatomyositis

Rapidly Progressive Kidney Failure in a Patient with Longstanding Juvenile Dermatomyositis

Immunofluorescence analyses of respiratory epithelial cells aid the diagnosis of nephronophthisis.

Nephronophthisis (NPH) comprises a heterogeneous group of inherited renal ciliopathies clinically characterized by progressive kidney failure. So far, definite diagnosis is based on molecular testing only. Here, we studied the feasibility of NPHP1 and NPHP4 immunostaining of nasal epithelial cells to secure and accelerate the diagnosis of NPH. Samples of 86 individuals with genetically determined renal ciliopathies were analyzed for NPHP1 localization using immunofluorescence microscopy (IF). A sub-cohort of 35 individuals was also analyzed for NPHP4 localization. Western blotting was performed to confirm IF results. NPHP1 and NPHP4 were both absent in all individuals with disease-causing NPHP1 variants including one with a homozygous missense variant (c.1027G > A; p.Gly343Arg) formerly classified as a "variant of unknown significance." In individuals with an NPHP4 genotype, we observed a complete absence of NPHP4 while NPHP1 was severely reduced. IF results were confirmed by immunoblotting. Variants in other genes related to renal ciliopathies did not show any impact on NPHP1/NPHP4 expression. Aberrant immunostaining in two genetically unsolved individuals gave rise for a further genetic workup resulting in a genetic diagnosis for both with disease-causing variants in NPHP1 and NPHP4, respectively. IF of patient-derived respiratory epithelial cells may help to secure and accelerate the diagnosis of nephronophthisis-both by verifying inconclusive genetic results and by stratifying genetic diagnostic approaches. Furthermore, we provide in vivo evidence for the interaction of NPHP1 and NPHP4 in a functional module.

MYH9-related disease with a normal platelet count.

MYH9-related disease (MYH9-RD) is characterized by congenital macrothrombocytopenia, progressive kidney failure, and sensorineural hearing loss. We describe a patient with MYH9-RD and a normal platelet count. A 13-year-old boy with a normal platelet count presented with proteinuria and hematuria and underwent a kidney biopsy. Light microscopy showed mild mesangial matrix expansion. Electron microscopy showed thinning of the glomerular basement membrane and splitting of the lamina densa. A tentative diagnosis of Alport syndrome was made. Unexpectedly, genetic analysis revealed a de novo MYH9 gene variant (p.Gln1068_Leu1074dup). A peripheral blood smear examination showed giant platelets and leukocyte inclusion bodies, confirming a diagnosis of MYH9-RD. In summary, we described a patient with MYH9-RD without thrombocytopenia who showed glomerular basement membrane abnormalities similar to Alport syndrome. Peripheral blood smear examinations may be helpful for an appropriate diagnosis of MYH9-RD, even in patients with proteinuria and a normal platelet count.

Progressive Kidney Failure by Angiotensinogen Inactivation in the Germline.

Autosomal recessive renal tubular dysgenesis is a rare, usually fatal inherited disorder of the renin-angiotensis system (RAS). Herein, we report an adolescent individual experiencing an unknown chronic kidney disease and aim to provide novel insights into disease mechanisms. Exome sequencing for a gene panel associated with renal disease was performed. The RAS was assessed by comprehensive biochemical analysis in blood. Renin expression was determined in primary tubular cells by quantitative polymerase chain reaction and in situ hybridization on kidney biopsy samples. Allele frequencies of heterozygous and biallelic deleterious variants were determined by analysis of the Genomics England 100,000 Genomes Project. The patient was delivered prematurely after oligohydramnios was detected during pregnancy. Postnatally, he recovered from third-degree acute kidney injury but developed chronic kidney disease stage G3b over time. Exome sequencing revealed a previously reported pathogenic homozygous missense variant, p.(Arg375Gln), in the AGT (angiotensinogen) gene. Blood AGT concentrations were low, but plasma renin concentration and gene expression in kidney biopsy, vascular, and tubular cells revealed strong upregulation of renin. Angiotensin II and aldosterone in blood were not abnormally elevated. Renal tubular dysgenesis may present as chronic kidney disease with a variable phenotype, necessitating broad genetic analysis for diagnosis. Functional analysis of the RAS in a patient with AGT mutation revealed novel insights regarding compensatory upregulation of renin in vascular and tubular cells of the kidney and in plasma in response to depletion of AGT substrate as a source of Ang II (similarly observed with hepatic AGT silencing for the treatment of hypertension).

Apical tubular complement activation and the loss of kidney function in proteinuric kidney diseases.

Many kidney diseases are associated with proteinuria. Since proteinuria is independently associated with kidney function loss, anti-proteinuric medication, often in combination with dietary salt restriction, comprises a major cornerstone in the prevention of progressive kidney failure. Nevertheless, complete remission of proteinuria is very difficult to achieve, and most patients with persistent proteinuria slowly progress toward kidney failure. It is well-recognized that proteinuria leads to kidney inflammation and fibrosis via various mechanisms. Among others, complement activation at the apical side of the proximal tubular epithelial cells is suggested to play a crucial role as a cause of progressive loss of kidney function. However, hitherto limited attention is given to the pathophysiological role of tubular complement activation relative to glomerular complement activation. This review aims to summarize the evidence for tubular epithelial complement activation in proteinuric kidney diseases in relation to loss of kidney function.

#626 C3 glomerulonephritis and thrombotic microangiopathy—a prospective observational study

Abstract Background and Aims Complement mediated TMA (cTMA) and complement component 3 glomerulonephritis (C3GN) are two distinct complement mediated kidney diseases. cTMA is characterized by acute kidney injury, thrombocytopenia and microangiopathic hemolytic anemia. C3GN results from uncontrolled activation of the alternative complement pathway leading to the deposition of C3 in the glomerulus. We sought to describe characteristic differences between these two conditions in a large cohort of patients from Bengaluru, India. Method All cases of cTMA and kidney biopsy proven C3GN from 2019-2022 at a tertiary care centre in India were included. Patients with C3GN had persistently low C3 for more than 12 weeks and no identifiable source of infection. All patients received protocolized medical therapy; patients with C3GN were treated with steroids and cyclophosphamide, while those with complement mediated TMA received plasmapheresis in addition to cyclophosphamide and steroids. Protocolised medical management (renin-angiotensin-aldosterone inhibition and diuretics) was provided in both the cases. Demographic, clinical and lab parameters were reported and compared. Results A total of 25 cTMA cases and 19 C3GN cases were included in the study. Both C3GN (52.7%) and cTMA (48%) were more common in males. Patients with C3GN typically presented in the third decade of life while cTMA cases presented in the fourth decade. Secondary hypertension was common in the cTMA group (92% vs 78.9%, compared to C3GN). 60% of patients with cTMA had either recent or current infection compared to 21.1% of C3GN patients (P = 0.04). The majority of cTMA cases had IFTA of &amp;lt;25% (84%) compared to C3GN (57.9%) although this was not statistically significant. Both C3GN and cTMA most commonly presented as rapidly progressive kidney failure and acute kidney injury. A total of 76% of patients in the cTMA group required kidney replacement therapy as compared to 47.4% in the C3GN group (P = 0.009). 44% of cTMA cases had anti factor H antibody positivity compared to 15.8% of C3GN patients (P = 0.02). Finally, 44% of cases in cTMA group had complete recovery compared to 47.4% in C3GN group at the end of 2.8 years of followup. Conclusion Although both conditions result from dysregulation of the alternative pathway, there are several important clinical characteristic differences between patients with cTMA and C3GN including presence or absence of secondary hypertension, concurrent infection, anti-factor H positivity and requirement of kidney replacement therapy. This information may be helpful to inform both diagnosis and prognosis for patients presenting with a complement mediated kidney disease.

#2232 Personalized kidney replacement therapy in critically ill patients: unity makes strength!

Abstract Background and Aims The complexity of the critically ill patient with kidney disease has increased in recent years. A holistic and multidisciplinary approach is, therefore, necessary in order to provide the best therapeutic guidance. Multiple modalities of kidney replacement therapies (KRT) are available in this setting, namely continuous kidney replacement therapies (CKRTs) and hybrid therapies, also such as sustained low-efficiency dialysis (SLED) and slow continuous ultrafiltration (SCUF). These techniques can be used in conjunction with other extracorporeal clearance therapies such as plasmapheresis (PF), and immunoadsorption (IA). Their prescription must be individualized according to the characteristics of each patient. In our hospital all KRT and extracorporeal techniques used are reviewed daily by a nephrologist. This study aims to describe the 20-year experience of our centre in individualized KRT prescription in intensive care. Methods A retrospective cohort, single centre study was conducted. We reviewed adult patients (age ≥18 years) admitted in all the ICUs of our hospital centre between January 2002 and December 2022, who required a KRT. We aimed to describe demographic data, different stages of kidney disease [AKI, AKI in CKD, chronic hemodialysis (HD), peritoneal dialysis (PD), kidney transplant (KT), rapidly progressive kidney failure (RPKF), other causes], the KRT used and the main outcomes. Results During the study period, 1578 patients who required a KRT were admitted to the ICU. Median age was 65 (IQR: 45-81) years old and 59.9% were male. Among these patients 715 (45.3%) had AKI, 380 (24.1%) were in HD, 315 (20%) had AKI in CKD, 130 (8.2%) had a KT and 31 (2%) were in PD. Four patients had RPKF and 3 patients had other causes for KRT, such as hyperammonemia and sodium valproate poisoning. The main KRT performed were: SLED—1365 (86.5%) patients; continuous venovenous hemodiafiltration (cvvHDF)—120 (7.6%) patients; SLED + cvvHDF—66 (4.2%). Other KRT executed were SLED + PF (11 patients), continuous venovenous hemofiltration (cvvHF) (8 patients) and SCUF (2 patients). Among all patients mortality rate was 42.3%, 33% had renal recovery and 7.4% started chronic HD. In AKI group the median age was 64 (IQR: 48-80) years and 56.3% were male. 576 (80.7%) performed SLED, 91 (12.7%) did cvvHDF and 36 (5.0%). Mortality rate was of 52.1%, renal recovery 45% and 2.9% started chronic HD. Conclusion Our ICU multidisciplinary approach model with a critical care nephrology specialists team translates into a large amount of accumulated experience with SLED. Our results are comparable to centres that predominantly use CKRTs. The range of different techniques used reflects the fact that KRT has become a complex treatment for critically ill patients, which allows for the prescription to be precisely tailored to the different daily clinical needs.

#1701 IgA nephropathy in numbers: the experience of a single center

Abstract Background and Aims IgA nephropathy is probably the most common glomerular disease worldwide and kidney histology is recognized to significantly impact the risk of progressive kidney failure. Method This is a retrospective cohort study of adult patients diagnosed with biopsy-proven IgA nephropathy during the last decade in the nephrology department of a tertiary hospital. Results In total, 75 patients with biopsy-proven IgA nephropathy were identified and data from 53 of them were analyzed [mean age 48 ± 16 [SD] years, 81% males, 60% hypertensives, 19% diabetics, baseline serum creatinine 2.03 ± 1.80 mg/dl, baseline estimated glomerular filtration rate (eGFR) 60.9 ± 31.4 ml/min/1.73 m2, baseline proteinuria 2.76 ± 2.44 gr/24 h]. Eventually, 6 patients were submitted to chronic dialysis. 50% of the patients received RAAS blockers and 14% received SGLT2-inhibitors. The most frequently used immunosuppression regimens were glucocorticoids alone (33%), glucocorticoids plus cyclophosphamide and azathioprine (13%), budesonide (9%). Relapse was identified in 9% of the patients and it was treated with glucocorticoids alone or budesonide. 25% of the patients had elevated serum IgA levels. Crescents were identified in 36% of the patients and interstitial and mesangial inflammation were observed in 83% and 64% of the patients respectively. Approximately all of the patients had arterial vessels with hyalinosis or fibroelastosis. Concerning immunofluorescence, the dominant findings were IgA, IgM, c3, λ light chain, while all other components were merely found. The median duration of follow-up was 2 years and the follow-up minus baseline serum creatinine, eGFR, and proteinuria differences were 0.35 ± 1.77 mg/dl, −4.0 ± 22.2 ml/min/1.73 m2, and −1.46 ± 2.39 gr/24 h, respectively. Median follow-up minus baseline eGFR was higher for diabetics (1.5 vs 0 ml/min/1.73 m2, p = 0.04). Participants receiving treatment with glucocorticoids were found to present a reduction of serum creatinine during follow-up (follow-up minus baseline median serum creatinine −0.1 vs 0.2 mg/dl for participants receiving vs not receiving glucocorticoids, p = 0.02) and a non-reduction of eGFR (follow-up minus baseline median eGFR 0 vs −3 ml/min/1.73 m2 for participants receiving vs not receiving glucocorticoids, p = 0.01). Participants receiving treatment with SGLT2 inhibitors were also found to have stable median eGFR during follow-up (follow-up minus baseline median eGFR 0 vs −11 ml/min/1.73 m2 for participants receiving vs not receiving SGLT2 inhibitors, p = 0.01). In multivariable linear regression analysis, follow-up minus baseline serum creatinine was independently associated with baseline proteinuria (β = 0.38, p &amp;lt; 0.01), administration of glucocorticoids (β= −1.23, p = 0.01), and the S component of MEST-c score (β = 1.27, p = 0.04), after adjustment for age, sex, baseline serum creatinine, diabetes, hypertension, MEST-c score, and percentage of interstitial fibrosis. In multivariable linear regression analysis, follow-up minus baseline eGFR was independently associated with baseline eGFR (β= −0.43, p &amp;lt; 0.01), baseline proteinuria (β= −2.54, p &amp;lt; 0.05), and hypertension status (β= −18.93, p = 0.02), after adjustment for age, sex, diabetes, treatment with glucocorticoids, MEST-c score, and percentage of interstitial fibrosis. Conclusion These preliminary data indicate that patients with IgA nephropathy who were treated with glucocorticoids or SGLT2 inhibitors present better course concerning the renal function, and the S component of MEST-c score was the only element of the kidney biopsy associated with the kidney outcome.

Detecting and managing the patient with chronic kidney disease in primary care: A review of the latest guidelines.

Chronic kidney disease (CKD) is a major global health problem, affecting about 9.5% of the population and 850 million people worldwide. In primary care, most CKD is caused by diabetes and/or hypertension, but a substantial proportion of cases may have alternative causes. During the early stages, CKD is asymptomatic, and many people are unaware that they are living with the disease. Despite the lack of symptoms, CKD is associated with elevated risks of cardiovascular disease, progressive kidney disease, kidney failure and premature mortality. Risk reduction strategies are effective and cost-effective but require early diagnosis through testing of the estimated glomerular filtration rate and albuminuria in high-risk populations. Once diagnosed, the treatment of CKD centres around lifestyle interventions, blood pressure and glycaemic control, and preventative treatments for cardiovascular disease and kidney disease progression. Most patients with CKD should be managed with statins, renin-angiotensin-aldosterone system inhibitors and sodium-glucose cotransporter-2 inhibitors. Additional treatment options to reduce cardiorenal risk are available in patients with diabetes, including glucagon-like peptide-1 receptor agonists and non-steroidal mineralocorticoid receptor antagonists. The Kidney Failure Risk Equation is a new tool that can support the identification of patients at high risk of progressive kidney disease and kidney failure and can be used to guide referrals to nephrology. This review summarizes the latest guidance relevant to managing adults with, or at risk of, CKD and provides practical advice for managing patients with CKD in primary care.

Autosomal dominant hypercalciuric hypocalcaemia: the calcium-sensing receptor in renal calcium homeostasis and the impact of renal transplantation.

Calcium-sensing receptors (CaSRs) are G protein-coupled receptors that help maintain Ca2+ concentrations, modulating calciotropic hormone release (parathyroid hormone (PTH), calcitonin and 1,25-dihydroxyvitamin D) by direct actions in the kidneys, gastrointestinal tract and bone. Variability in population calcium levels has been attributed to single nucleotide polymorphisms in CaSR genes, and several conditions affecting calcium and phosphate homeostasis have been attributed to gain- or loss-of-function mutations. An example is autosomal dominant hypercalciuric hypocalcaemia, because of a missense mutation at codon 128 of chromosome 3, as reported in our specific case and her family. As a consequence of treating symptomatic hypocalcaemia as a child, this female subject slowly developed progressive end-stage kidney failure because of nephrocalcinosis and nephrolithiasis. After kidney transplantation, she remains asymptomatic, with decreased vitamin D and elemental calcium requirements, stable fluid and electrolyte homeostasis during intercurrent illnesses and has normalised urinary calcium and phosphate excretion, reducing the likelihood of hypercalciuria-induced graft impairment. We review the actions of the CaSR, its role in regulating renal Ca2+ homeostasis along with the impact of a proven gain-of-function mutation in the CaSR gene resulting in autosomal dominant hypercalciuric hypocalcaemia before and after kidney transplantation.

Clinicopathological features and medium-term outcomes of histologic variants of primary focal segmental glomerulosclerosis in adults: A retrospective study.

The Columbia classification identified five histological variants of focal segmental glomerulosclerosis (FSGS). The prognostic significance of these variants remains controversial. To evaluate the relative frequency, clinicopathologic characteristics, and medium-term outcomes of FSGS variants at a single center in Pakistan. This retrospective study was conducted at the Department of Nephrology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan on all consecutive adults (≥ 16 years) with biopsy-proven primary FSGS from January 1995 to December 2017. Studied subjects were treated with steroids as a first-line therapy. The response rates, doubling of serum creatinine, and kidney failure (KF) with replacement therapy were compared between histological variants using ANOVA or Kruskal Wallis, and Chi-square tests as appropriate. Data were analyzed by SPSS version 22.0. P-value ≤ 0.05 was considered significant. A total of 401 patients were diagnosed with primary FSGS during the study period. Among these, 352 (87.7%) had a designated histological variant. The not otherwise specified (NOS) variant was the commonest, being found in 185 (53.9%) patients, followed by the tip variant in 100 (29.1%) patients. Collapsing (COL), cellular (CEL), and perihilar (PHI) variants were seen in 58 (16.9%), 6 (1.5%), and 3 (0.7%) patients, respectively. CEL and PHI variants were excluded from further analysis due to small patient numbers. The mean follow-up period was 36.5 ± 29.2 months. Regarding response rates of variants, patients with TIP lesions achieved remission more frequently (59.5%) than patients with NOS (41.8%) and COL (24.52%) variants (P < 0.001). The hazard ratio of complete response among patients with the COL variant was 0.163 [95% confidence interval (CI): 0.039-0.67] as compared to patients with NOS. The TIP variant showed a hazard ratio of 2.5 (95%CI: 1.61-3.89) for complete remission compared to the NOS variant. Overall, progressive KF was observed more frequently in patients with the COL variant, 43.4% (P < 0.001). Among these, 24.53% of patients required kidney replacement therapy (P < 0.001). The hazard ratio of doubling of serum creatinine among patients with the COL variant was 14.57 (95%CI: 1.87-113.49) as compared to patients with the TIP variant. In conclusion, histological variants of FSGS are predictive of response to treatment with immunosuppressants and progressive KF in adults in our setup.

An Update on Current Therapeutic Options in IgA Nephropathy.

Immunoglobulin A nephropathy (IgAN) remains the leading cause of primary glomerular disease worldwide. Outcomes are poor with high rates of progressive chronic kidney disease and kidney failure, which contributes to global healthcare costs. Although this disease entity has been described, there were no disease-specific treatments until recently, with the current standard of care focusing on optimal supportive measures including lifestyle modifications and optimization of the renin-angiotensin-aldosterone blockade. However, with significant advances in the understanding of the pathogenesis of IgAN in the past decade, and the acceptance of surrogate outcomes for accelerated drug approval, there have been many new investigational agents tested to target this disease. As these agents become available, we envision a multi-pronged treatment strategy that simultaneously targets the consequences of ongoing nephron loss, stopping any glomerular inflammation, inhibiting pro-fibrotic signals in the glomerulus and tubulo-interstitium, and inhibiting the production of pathogenic IgA molecules. This review is an update on a previous review published in 2021, and we aim to summarize the developments and updates in therapeutic strategies in IgAN and highlight the promising discoveries that are likely to add to our armamentarium.

A 6-year review of acute post-streptococcal glomerulonephritis at a public children’s hospital in Cape Town, South Africa

BackgroundAcute post-streptococcal glomerulonephritis (APSGN) is the most common cause of acute nephritis in children globally and, in some cases, may be associated with progressive kidney injury and failure, cumulating in the need for long-term dialysis and/or kidney transplantation.MethodsOur retrospective study describes the occurrence of APSGN among children (< 14 years) admitted to a tertiary children’s hospital in Cape Town, South Africa, from January 2015 to December 2020.ResultsOf 161 children who presented with acute nephritis (haematuria, oedema, oliguria, and hypertension), 100 met the inclusion criteria. Demographic, clinical features, laboratory findings, management, and outcome data were collected. APSGN was defined by the clinical presentation of at least two clinical signs of acute nephritis, and low serum complement 3 (C3) level or evidence of a recent streptococcal infection. Most cases of APSGN were associated with streptococcal skin infections: 55/100 (55%); 10/100 (10%) children presented with hypertensive seizures; C3 levels were low in 86/92 (93.5%) children; 94/94 (100%) children had elevated anti-deoxyribonuclease-B (anti-DNase-B) levels; and 80/94 (85%) also had elevated anti-streptolysin O titre (ASOT) at presentation. Eleven (11%) children had a percutaneous kidney biopsy; 4/11 (36%) showed histological features of post-infectious nephritis, and 7/11(64%) also had crescentic glomerulonephritis with immune complex deposits. Sixty-two (62%) children confirmed recovered, and five (5%) progressed to kidney failure, but 29 presumed recovered as they did not return for follow-up to our institution.ConclusionsChildhood APSGN remains an important health problem in South Africa (SA) with favourable outcomes in most, apart from those with crescentic glomerulonephritis who progressed to kidney failure.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

Chronic Kidney Disease: Decreasing Serum Klotho Levels Predict Adverse Renal and Vascular Outcomes.

Background and Objectives: Soluble alpha Klotho (s.Klotho) is an emerging marker for chronic kidney disease (CKD) prognosis. The objective was to study the association between s.Klotho and CKD-related decrease in glomerular filtration rate (GFR), bone and vascular damage. Method: A total of 118 patients with CKD stage 2-4 were enrolled and 107 patients continued in the study. Clinical and laboratory parameters were recorded at time of enrollment and 12 months. A double sandwich ELISA for s.Klotho was recorded in controls (n = 25) and patients' serum samples at 6 months (n = 107) and 12 months (n = 102). Primary endpoints like 40% or more fall in GFR, a requirement for renal replacement therapy (RRT), and death with different grades of s.Klotho deficiency were studied. Results: Of the 107 patients (80 male and 27 female), mean s.Klotho was 3.46 ng/mL (02.3-04.2). The GFR fall was significantly different (p value < 0.0001) in the different grades of s.Klotho deficiency with Grade 4 s.Klotho deficiency (0.1-2.99 ng/mL) having the maximum fall of GFR at 9.2 mL/min/1.73 m2 (04.8-12.0) and minimum in Grade 2 (3-5.99 ng/mL) at 1.35 mL/min/1.73 m2 (03.0-02.75). The Ankle Brachial Pressure Index positively correlated with s.Klotho and the correlation coefficient was 0.536 (0.382-0.662) (p < 0.001). The carotid intimal medial thickness negatively correlated with s.Klotho and the correlation coefficient was -0.712 (95% CI: -0.797--0.601, p < 0.001). All five deaths had s.Klotho Grade 4 (severe) deficiency. The event-free survival rate was maximum (100%) in Grade 2 Klotho deficiency and lowest (55%) in Grade 4 s.Klotho deficiency. Conclusions: s.Klotho levels decreased significantly in patients with progressive kidney failure. s.Klotho levels significantly correlated with the presence of vascular disease. Death and need for RRT were significantly more in patients with severe s.Klotho deficiency.

Characteristics and predictors of chronic kidney disease in children with myelomeningocele: a nationwide cohort study.

Myelomeningocele (MMC) is highly prevalent in developing countries, and MMC-related neurogenic bladder is an important cause of childhood chronic kidney disease (CKD). This nationwide study aimed to evaluate demographic and clinical features of pediatric patients with MMC in Turkey and risk factors associated with CKD stage 5. Data from children aged 0-19years old, living with MMC in 2022, were retrospectively collected from 27 pediatric nephrology centers. Patients > 1year of age without pre-existing kidneyabnormalities were divided into five groups according to eGFR; CKD stages 1-5. Patients on dialysis, kidney transplant recipients, and those with eGFR < 15ml/min/1.73 m2 but not on kidney replacement therapy at time of study constituted the CKD stage 5 group. A total of 911 (57.8% female) patients were enrolled, most of whom were expectantly managed. Stages 1-4 CKD were found in 34.3%, 4.2%, 4.1%, and 2.4%, respectively. CKD stage 5 was observed in 5.3% of patients at median 13years old (range 2-18years). Current age, age at first abnormal DMSA scan, moderate-to-severe trabeculated bladder on US and/or VCUG, and VUR history were independent risk factors for development of CKD stage 5 (OR 0.752; 95%; CI 0.658-0.859; p < 0.001; OR 1.187; 95% CI 1.031-1.367; p = 0.017; OR 10.031; 95% CI 2.210-45.544; p = 0.003; OR 2.722; 95% CI 1.215-6.102; p = 0.015, respectively). Only eight CKD stage 5 patients underwent surgery related to a hostile bladder between 1 and 15years old. MMC-related CKD is common in childhood in Turkey. A proactive approach to neurogenic bladder management and early protective surgery in selected cases where conservative treatment has failed should be implemented to prevent progressive kidney failure in the pediatric MMC population in our country.