Search Results (38)

Steroid-resistant nephrotic syndrome (SRNS) in childhood frequently reflects monogenic podocytopathies in which immunosuppression is ineffective. Biallelic variants in MYO1E, encoding the class I myosin Myo1E, cause a distinctive form of focal segmental glomerulosclerosis (FSGS) often accompanied by “Alport-like” multilamination of the glomerular basement membrane (GBM). Early recognition has therapeutic and prognostic implications. A previously healthy 4-year-old boy presented with generalized edema and nephrotic-range proteinuria. Glucocorticoids induced no remission; sequential calcineurin inhibition (cyclosporine, then tacrolimus) and a single dose of ofatumumab yielded only transient, partial reductions in proteinuria. A first biopsy elsewhere showed FSGS with nonspecific IgM/C3 trapping; electron microscopy (EM) was not performed. At age 10, repeat biopsy with EM revealed ~30% segmental foot-process effacement, focal GBM thickening (to 1740 nm), irregular lamina densa multilamination, and lamellar duplications without immune-complex deposits—features highly suggestive of hereditary GBM disease. Targeted sequencing identified compound-heterozygous MYO1E variants segregating in trans: a canonical splice-donor change (c.2785+1G>A) and a frameshift (c.3094_3097del; p.Thr1032Profs*73). Each parent was an unaffected heterozygous carrier; the sibling was negative. Supportive therapy with ramipril was continued. At last follow-up (January 2025), renal function was normal (serum creatinine 0.5 mg/dL; creatinine clearance 122 mL/min) with stable sub-nephrotic proteinuria (0.52 g/day; 16 mg/m² per hour) and normotension. This case broadens clinicopathologic recognition of MYO1E-associated nephropathy and highlights the teaching point that Alport-like GBM changes are not pathognomonic for type IV collagen disorders but may signal defects in podocyte cytoskeletal anchoring. Full article

Mouse models for “definitive” polyomavirus nephropathy with lytic viral replication and end-organ disease (PyVN) do not exist. We aimed at defining a PyVN model in Black-Swiss mice (n = 126) by injecting newborn animals with murine polyomavirus (strain A2; 1 × 10⁵ plaque forming units) that led in all mice to a productive intrarenal infection with genetically stable, episomal MuPyV lacking latency. Animals were monitored and morphologic, immunohistochemical, molecular, genetic, and immunological analyses were conducted. Results: Within 3–6 weeks peak PyVN developed characterized by acute tubular injury, lytic replication in up to 14% of tubules (mainly collecting ducts/distal nephrons), high viral gene coverage (up to 3589 viral DNA reads/cell equivalent) and RNA expression (up to 9317 VP1-RNA reads/10⁷ RNA reads), inflammation, DNAemia, and-uria. MuPyV doubling times were high early post-infection (urine: 0.17 day–1.61 day) followed by steady slow viral clearance post day 28 (urine, half-life: 9.90 days). By 54 weeks PyVN had morphologically cleared (no chronic tissue injury) with only qPCR evidence of residual MuPyV in 17% of kidneys/mice. Infection induced an IgM/IgG response (peak plasma IgG titer at 7–30 weeks 1:20,480; low IgG titers in 92% of mice at end of follow-up after one year). During infection, episomal MuPyV remained genetically stable, without significant alterations that could have modified the course of PyVN. The mouse model resembles “definitive” PyVN in humans. It is suited for research on the pathogenesis of PyVN including virally induced tubular injury and immunologic interactions. It facilitates in vivo studies of therapeutic interventions aimed at blocking lytic intrarenalPyV replication. Full article

Diabetic nephropathy (DN) is the most common cause of kidney failure worldwide. Mesenchymal stromal cells (MSCs) have demonstrated promise for treating DN by promoting kidney repair and regulating inflammation. Allogeneic (Allo)-MSCs may have similar or superior anti-inflammatory effects to autologous (Auto)-MSCs but also have potential to elicit adverse immune responses due to major histocompatibility complex (MHC) mismatches. To better understand how MSC-delivered allo-antigens influence therapeutic effects of Allo-MSCs compared to Auto-MSCs in DN, lentiviral transduction was used to generate adipose-derived MSCs (ADSCs) from DBA/2J (H-2^d) mice which expressed an allogeneic class I MHC protein (H-2K^b). H-2K^b-ADSCs were injected intravenously into male DBA/2J mice at 11 and 13 weeks after initiation of diabetes, and their effects on renal functional and structural indices were compared at week 15 with those of diabetic DBA/2J recipients of vehicle alone or of empty vector-transduced DBA/2J ADSCs (EV-ADSCs). Both EV-ADSCs and H-2K^b-ADSCs resulted in reduced kidney/total body weight ratio, blood urea nitrogen (BUN), urine albumin creatinine ratio (uACR), mesangial matrix expansion (MME) and renal fibrosis compared to vehicle alone, without influencing glycemia or survival. However, H-2K^b-ADSCs recipients had greater reductions in BUN and uACR, reduced intra-renal myeloid cell infiltration, increased splenic regulatory T cell (Treg) proportions and increased intra-renal Treg infiltration and FOXP3 and IL-10 mRNA. Nonetheless, recipients of H-2K^b-ADSCs also had decreased splenic CD4/CD8 T cell ratios, increased circulating anti-H-2K^b IgG antibodies and histological and biochemical evidence of inflammatory liver injury. These novel findings demonstrated that ADSCs expressing an MHC-I allo-antigen had superior beneficial effects on DN than fully autologous ADSCs. Improved DN severity was associated with immune modulation, including Treg enhancement, but also had potentially detrimental immunological effects in mice with established diabetes. The results highlight the need for further investigation of the immune modulatory effects of Allo-MSCs in diabetes and its organ-specific complications. Full article

Background and Objectives: IgA nephropathy represents the most prevalent form of primary glomerulonephritis around the world, with significant heterogeneity in management strategies and outcomes. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of pharmacological interventions for IgA nephropathy. Materials and Methods: We searched multiple databases through June 2025, identifying randomized controlled trials and observational studies evaluating pharmacological treatments in biopsy-proven IgA nephropathy. Primary outcomes included proteinuria reduction and estimated glomerular filtration ration (eGFR) preservation. Secondary outcomes included hard kidney endpoints and safety parameters. Random-effects meta-analyses were performed with comprehensive risk–benefit assessments. Results: Twenty-five studies were included. B-cell/plasma-cell-targeted therapies showed significant proteinuria reduction (−34.0% [95% CI: −45.7, −22.3%]), complement pathway inhibitors demonstrated superior eGFR preservation (+5.8 mL/min/1.73 m²/year [95% CI: 2.4, 9.2]). Systemic corticosteroids showed observed hard outcome benefits (HR 0.37 [95% CI: 0.26, 0.52]) but highest adverse event risk (RR 3.28 [95% CI: 2.11, 5.09]). Novel agents showed projected favorable effects (B-cell: HR 0.38; complement: HR 0.42) pending validation. Conclusions: Novel targeted therapies, especially B-cell/plasma-cell-targeted agents and complement pathway inhibitors, show promising risk–benefit profiles. However, longer-term data and standardized eGFR slope reporting are needed to confirm these findings compared to other immunosuppressive agents. Full article

Objective: This study aimed to identify clinical and laboratory predictors of kidney involvement and disease relapse in pediatric patients with IgA vasculitis (Immunoglobulin A vasculitis, IgAV). Materials and Methods: A retrospective cohort study was conducted on 173 children diagnosed with IgAV at the Children’s Clinical Hospital of the Medical University of Warsaw between 2018 and 2022. Patients were categorized into groups based on renal involvement (IgAVN+ vs. IgAVN−) and disease recurrence. The analysis included demographic data, clinical manifestations, allergy history, presence of infection, duration of hospitalization, relapse occurrence, the interval between the first and second hospitalization, and laboratory markers. Results: Renal involvement was observed in 42% of cases, while disease recurrence occurred in 9.25% of patients. IgAVN+ patients were older, had longer hospital stays, and more frequently exhibited gastrointestinal symptoms, consistent with previous research. A history of allergic conditions was more prevalent in both the IgAVN+ and recurrence groups. An increase in IgA levels over time was associated with a higher risk of nephropathic development. Patients with recurrences had higher IgM levels and an elevated neutrophil-to-lymphocyte ratio (NLR) (p = 0.07). In the ROC (Receiver Operating Characteristic) analysis, a cutoff value of 1.67 for NLR (AUC 0.71; p = 0.0002; sensitivity 0.87; specificity 0.58) was identified as a risk factor for disease recurrence. Conclusions: Older age at disease onset, gastrointestinal involvement, and allergies are associated with renal involvement in pediatric IgAV. Immune dysregulation, reflected by elevated NLR and IgM, may contribute to disease recurrence. It is important to monitor changes in IgA levels over time, as an increase in IgA concentration is a risk factor for the development of nephropathy. Additionally, calculating the NLR is recommended, as it may indicate the probability of disease recurrence. Full article

Background & Objectives: Targeted-release budesonide (TRB) is the first approved agent aimed at targeting the early pathogenetic cascade in IgA nephropathy (IgAN). Materials and Methods: This prospective study included Caucasian IgAN patients diagnosed within the last 5 years, who had started a 10-month TRB treatment and were followed in the outpatient clinic. All participants had been on the maximal supportive care dose for at least the previous 6 months. Kidney function and proteinuria levels were recorded at the start of TRB treatment (T0) and at 3, 6, and 10 months (T3, T6, and T10, respectively), while urinary monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9) and clusterin (CLU) levels were measured at T0 and T3. Results: In the cohort of all patients (mean age 53.24 ± 12.76 years, estimated glomerular filtration rate (eGFR 52.84 ± 25.93 mL/min/1.73 m², proteinuria 2.84 ± 1.26 g/24 h), significant correlations were observed at T0 between MMP-9 and MCP-1 (r = 0.74, p = 0.004), MMP-9 and uCLU (r = 0.77, p = 0.002), and MCP-1 and uCLU (r = 0.65, p = 0.01). At T3, a significant correlation between MMP-9 and urinary CLU (uCLU) persisted (r = 0.71, p = 0.03). Higher MCP-1 (r = −0.560, p = 0.046) and MMP-9 (r = −0.330, p = 0.012) levels at T0 were associated with reduced proteinuria. Conversely, increased clusterin at T3 (r = 0.599, p = 0.031) was associated with worsening proteinuria. Conclusions: The treatment response to TRB was heterogeneous, with recent diagnosis (RD) patients showing improved kidney function and proteinuria, while older diagnosis (OD) patients exhibited worsening biomarkers and declining kidney function. Therefore, early interventions are crucial in IgAN patients. Finally, the biomarkers studied can be used prognostically to monitor disease progression. Full article

Soluble epoxide hydrolase (sEH) has previously been demonstrated to play an important part in kidney diseases by hydrolyzing renoprotective epoxyeicosatrienoic acids to their less active diols. However, little is known about the role of sEH in primary glomerular diseases. Here, we investigated the effects of sEH inhibition on proteinuria in primary glomerular diseases and the underlying mechanism. The expression of sEH in the renal tubules of patients with minimal change disease, IgA nephropathy, and membranous nephropathy was significantly increased. Renal sEH expression level was positively correlated with the 24 h urine protein excretion and negatively correlated with serum albumin. In the animal model of Adriamycin (ADR)-induced nephropathy, renal sEH mRNA and protein expression increased significantly. Pharmacological inhibition of sEH with AUDA effectively reduced urine protein excretion and attenuated renal pathological damage. Furthermore, sEH inhibition markedly abrogated the abnormal expressions of nephrin and desmin in glomerular podocytes induced by ADR. More importantly, AUDA treatment inhibited renal NF-κB activation and reduced TNF-α levels in rats with ADR-induced nephropathy. Overall, our findings suggest that sEH inhibition ameliorates renal inflammation and podocyte injury, thus reducing proteinuria and exerting renoprotective effects. Targeting sEH might be a potential strategy for the treatment of proteinuria in primary glomerular diseases. Full article

IgA nephropathy (IgAN) is the most common primary glomerular disease. Endothelin-1 (ET-1) is one of the strongest vasoconstrictor materials in the blood. The N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is associated with renal function and poor outcomes in chronic kidney disease (CKD). Serum endocan is a biomarker associated with proinflammatory cytokines, and the increase in the serum level plays a critical role in inflammatory, proliferative, and neovascularization processes and is associated with poor cardiovascular outcomes in patients with CKD too. Identifying high-risk patients using biomarkers could help to optimize their treatment. Ninety patients with biopsy-confirmed IgAN were included in the study (50 males/40 females, mean age: 54.9 ± 14.4 years). Serum endocan, ET-1, and NT-proBNP were measured by enzyme-linked immunosorbent assay kits. Echocardiography was performed, and carotid-femoral pulse wave velocity (cfPWV) was measured by SphygmoCor in this cross-sectional study. Patients were divided into two groups based on serum endocan median level (cut-off: 44 ug/L). There was significantly higher aorta systolic blood pressure (SBPao) (p = 0.013), NT-proBNP (p = 0.028), albumin/creatinine ratio (p = 0.036), and uric acid (p = 0.045) in the case of the higher endocan group compared to the lower. There was also significantly higher SBPao (p = 0.037) and NT-proBNP (p = 0.038) in the case of higher endothelin-1 (ET-1) levels compared to the lower (cut-off: 231 pg/mL) group by the two-sample t-test. Then, we divided the patients into two groups based on the eGFR (CKD 1–2 vs. CKD 3–5). The levels of serum endocan, NT-proBNP, cfPWV, SBPao, left ventricular mass index (LVMI), uric acid, and albuminuria were significantly higher in the CKD 3–5 group compared to the CKD 1–2 group. The serum endocan and NT-proBNP levels were significantly higher in the diastolic dysfunction group (p = 0.047, p = 0.015). There was a significant increase in serum endocan levels (CKD 1 vs. CKD 5; p = 0.008) with decreasing renal function. In IgAN, vascular biomarkers (endocan, ET-1) may play a role in endothelial dysfunction through vascular damage and elevation of SBPao. Serum endocan, ET-1, and NT-proBNP biomarkers may help to identify IgAN patients at high risk. Full article

Background and Objectives: Systemic-inflammation-based prognostic scores and hematological indices have shown value in predicting outcomes in various clinical settings. However, their effectiveness in predicting outcomes specifically for IgA nephropathy (IgAN) and membranous nephropathy (MN), the most common primary glomerular diseases diagnosed by kidney biopsy, has not been thoroughly investigated. Materials and Methods: We conducted a retrospective, observational study involving 334 adult patients with biopsy-proven IgAN (196 patients) and MN (138 patients) from January 2008 to December 2017 at a tertiary center. We assessed six prognostic scores [Glasgow prognostic score (GPS), modified GPS (mGPS), prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-C-reactive protein ratio (LCRP)] and two hematological indices [red blood cell distribution width (RDW), platelet distribution width (PDW)] at diagnosis and examined their relationship with kidney and patient survival. Results: End-stage kidney disease (ESKD) occurred more frequently in the IgAN group compared to the MN group (37% vs. 12%, p = 0.001). The mean kidney survival time was 10.7 years in the IgAN cohort and 13.8 years in the MN cohort. After adjusting for eGFR and proteinuria, lower NLR and higher LCRP were significant risk factors for ESKD in IgAN. In the MN cohort, no systemic-inflammation-based scores or hematological indices were associated with kidney survival. There were 38 deaths (19%) in the IgAN group and 29 deaths (21%) in the MN group, showing no significant difference in mortality rates. The mean survival time was 13.4 years for the IgAN group and 12.7 years for the MN group. In the IgAN group, a lower PLR was associated with a higher mortality after adjusting for age, the Charlson comorbidity score, eGFR, and proteinuria. In patients with MN, higher NLR, PLR, and RDW were associated with increased mortality. Conclusions: NLR and LCRP are significant predictors of ESKD in IgAN, while PLR is linked to increased mortality. In MN, NLR, PLR, and RDW are predictors of mortality but not kidney survival. These findings underscore the need for disease-specific biomarkers and indicate that systemic inflammatory responses play varying roles in the progression and outcomes of these glomerular diseases. Future studies on larger cohorts are necessary to validate these markers. Full article

Uncovering the function of understudied G protein-coupled receptors (GPCRs) provides a wealth of untapped therapeutic potential. The poorly understood adhesion GPCR Gpr126 (Adgrg6) is widely expressed in developing kidneys. In adulthood, Gpr126 expression is enriched in parietal epithelial cells (PECs) and epithelial cells of the collecting duct and urothelium. Whether Gpr126 plays a role in kidney disease remains unclear. Here, we characterized Gpr126 expression in diseased kidneys in mice, rats, and humans. RT-PCR data show that Gpr126 expression is altered in kidney disease. A quantitative RNAscope^® analysis utilizing cell type-specific markers revealed that Gpr126 expression upon tubular damage is mainly increased in cell types expressing Gpr126 under healthy conditions as well as in cells of the distal and proximal tubules. Upon glomerular damage, an increase was mainly detected in PECs. Notably, Gpr126 expression was upregulated in an ischemia/reperfusion model within hours, while upregulation in a glomerular damage model was only detected after weeks. An analysis of kidney microarray data from patients with lupus nephritis, IgA nephropathy, focal segmental glomerulosclerosis (FSGS), hypertension, and diabetes as well as single-cell RNA-seq data from kidneys of patients with acute kidney injury and chronic kidney disease indicates that GPR126 expression is also altered in human kidney disease. In patients with FSGS, an RNAscope^® analysis showed that GPR126 mRNA is upregulated in PECs belonging to FSGS lesions and proximal tubules. Collectively, we provide detailed insights into Gpr126 expression in kidney disease, indicating that GPR126 is a potential therapeutic target. Full article

Background: IgA nephropathy (IgAN) is associated with chronic inflammation. Platelet-related parameters, such as the platelet (PLT) count, platelet-to-albumin ratio (PAR), and platelet-to-lymphocyte ratio (PLR), were examined as potential prognostic indicators for renal and cardiovascular (CV) outcomes in IgAN. We were interested in whether platelet-related parameters are risk factors for ESKD and CV events in IgAN patients. Methods: In a monocentric retrospective study, 124 IgAN patients were divided into two groups based on the cut-off value of the PAR. All-cause mortality, major CV events, and end-stage renal disease were the primary combined endpoints. Secondary endpoints, such as CV or renal endpoints, were also analyzed separately. Results: The patients’ mean age was 43.7 ± 13.5 years, and the follow-up time was 124 ± 67 months. The K-M curve showed that the PLR, PAR, and PLT were strongly associated with primary combined (p = 0.002, p = 0.004, p = 0.001) and renal outcomes (p < 0.001, p < 0.001, p < 0.001), but not with CV outcomes in IgAN. However, when combined with left ventricular hypertrophy (LVH) or metabolic syndrome (MetS), the PAR was found to be a significant predictor of both primary (p < 0.001, p < 0.001) and secondary outcomes (p = 0.001 and p = 0.038; p = 0.001 and p = 0.015). Additionally, the PLR correlated with albuminuria (r = −0.165, p = 0.033) and LVH (r = −0.178, p = 0.025), while PLT correlated with eGFR (r = 0.158, p = 0.040). Conclusions. Elevated PARs and PLRs may predict progression to end-stage kidney disease, but in combination with LVH and MetS, they were related to CV events in IgAN. The determination of PARs and PLRs can be useful and cost-effective parameters for assessing both cardiovascular and renal risks in IgAN. Full article

Routine immunofluorescence microscopy of glomerular immunodeposits in IgA nephropathy shows IgA, C3, and lambda light chains, and sometimes IgG, IgM, and kappa light chains. However, a previous study using high-resolution confocal microscopy showed IgG in all IgA nephropathy cases, likely representing autoantibodies specific for galactose-deficient IgA1. Here, we used high-resolution confocal microscopy to examine the composition of glomerular immunodeposits and colocalization of kappa and lambda light chains with IgA or IgG heavy chains in kidney-biopsy samples from twenty patients with IgA nephropathy, seventeen without IgG, and nine with no or trace kappa light chains by routine immunofluorescence microscopy. IgG was detected in all biopsies by high-resolution confocal microscopy. Single-optical-plane images showed similar colocalization of IgG heavy chains with kappa and lambda light chains. Colocalization of IgA heavy chains was greater with lambda light chains than with kappa light chains. Colocalization of IgG heavy chain with kappa light chains was higher than with lambda light chains in biopsies with endocapillary hypercellularity and crescents, i.e., biopsies with active lesions. We confirmed the utility of high-resolution confocal microscopy to detect components of glomerular immunodeposits not apparent on routine immunofluorescence microscopy and for colocalization of different components, potentially clarifying the pathogenesis of IgA nephropathy. Full article

Introduction: IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. Decreased glomerular filtration rate is a known risk factor for disease progression. Aim: We aimed to examine factors that may contribute to disease progression in children that present with impaired eGFR at the onset of IgAN. Materials and methods: Of the 175 patients with IgAN from the Polish Registry of Children with IgAN and IgAVN, 54 (31%) patients with IgAN who had an onset of renal function impairment (GFR < 90 mL/min) were eligible for the study. All of them were analyzed for initial symptoms (GFR according to Schwartz formula, creatinine, proteinuria, IgA, C3), renal biopsy result with assessment by Oxford classification, treatment used (R—renoprotection, P—prednisone+R, Aza—azathioprine+P+R, Cyc—cyclophosphamide+P+R, CsA—cyclosporine+P+R, MMF—mycophenolate mofetil+P+R), and distant follow-up. Based on the GFR score obtained at the end, patients were divided into two groups: A—GFR > 90 mL/min and B—GFR < 90 mL/min. Results: In the study group, the mean age of onset was 12.87 ± 3.57 years, GFR was 66.1 ± 17.3 mL/min, and proteinuria was 18.1 (0–967) mg/kg/d. Renal biopsy was performed 0.2 (0–7) years after the onset of the disease, and MESTC score averaged 2.57 ± 1.6. Treatment was R only in 39% of children, P+R in 20%, Aza+P+R in 28%, Cyc+P+R in 9%, CsA+P+R in 7%, and MMF+P+R in 3%. The length of the observation period was 2.16 (0.05–11) years. At the follow-up, Group A had 30 patients (56%) and Group B had 24 patients (44%). There were no significant differences in any of the other biochemical parameters (except creatinine) or proteinuria values between the groups and the frequency of the MESTC score ≥ 2 and <2 was not significantly different between Groups A and B. Patients with normal GFR at the follow-up (Group A) were significantly more likely to have received prednisone and/or immunosuppressive treatment than those in Group B (p < 0.05) Conclusions: In a population of Polish children with IgAN and decreased renal function at the onset of the disease, 56% had normal GFR in remote observation. The use of immunosuppressive/corticosteroids treatment in children with IgAN and impaired glomerular filtration rate at the beginning of the disease may contribute to the normalization of GFR in the outcome, although this requires confirmation in a larger group of pediatric patients. Full article

Kidney fibrosis is the hallmark of chronic kidney disease (CKD) and is characterized by an imbalanced extracellular matrix (ECM) remodeling. Collagen type III is one of the main ECM components of the interstitial matrix of the kidney. We hypothesized that measuring three biomarkers of collagen type III reflecting different aspects of this protein turnover (C3M, C3C, and PRO-C3) may provide different information about the fibrotic burden in patients with IgA nephropathy (IgAN). We examined a cohort of 134 patients with IgAN. The three collagen type III biomarkers were measured in serum (S) and in urine (U) samples taken on the same day before kidney biopsy was performed. Biopsies were evaluated for interstitial fibrosis and tubular atrophy, according to the Banff and MEST-C scores. S-PRO-C3 and S-C3C correlated with the degree of fibrosis in the biopsy, whereas U-C3M/Cr had an inverse correlation with fibrosis. U-C3M/Cr had the highest discrimination ability for advanced fibrosis, which was maintained after adjustment for the other collagen type III biomarkers, proteinuria, and serum creatinine. The data presented in this study indicate that measuring the different fragments of the same ECM protein and in different matrices provides a variety of information regarding pathological kidney tissue alterations in patients with IgAN. Full article

Renal disorders are uncommonly associated with IgM MGUS and Waldenström macroglobulinaemia (WM). Data are limited to large case series that suggest that related renal involvement occurs in 5% of patients with WM. Although uncommon, there is a much greater variety of renal pathologies associated with WM and IgM MGUS than that seen in patients with multiple myeloma, where cast nephropathy predominates. In WM, uncommonly direct infiltration of the renal system by lymphoma or cast nephropathy with a high light-chain level can occur. AL amyloidosis can present with nephrotic syndrome as a feature with IgM MGUS or WM. Cryoglobulinaemia and light-chain deposition disease are other important potential causes of renal impairment with IgM MGUS and WM. There are other rarer monoclonal gammopathy of renal significance (MGRS) conditions characterised by typically isolated kidney disease that are causally related to a B-cell or plasma-cell clonal disorder usually in a precancerous MGUS state, although in some renal pathologies, the association is less clear. Central to the majority of these diagnoses is the need for an accurate renal histological diagnosis, and management requires close joint working of renal and haematology teams. Full article