Light chain cast nephropathy (LCCN) in multiple myeloma often leads to severe and poorly reversible acute kidney injury. Severe renal impairment influences the allocation of chemotherapy and its tolerability; it also affects patient survival. Whether renal biopsy findings add to the clinical assessment in predicting renal and patient outcomes in LCCN is uncertain. We retrospectively reviewed clinical presentation, chemotherapy regimens, hematologic response, and renal and patient outcomes in 178 patients with biopsy-proven LCCN from 10 centers in Europe and North America. A detailed pathology review, including assessment of the extent of cast formation, was performed to study correlations with initial presentation and outcomes. Patients presented with a mean estimated glomerular filtration rate (eGFR) of 13 ± 11 mL/min/1.73 m2, and 82% had stage 3 acute kidney injury. The mean number of casts was 3.2/mm2 in the cortex. Tubulointerstitial lesions were frequent: acute tubular injury (94%), tubulitis (82%), tubular rupture (62%), giant cell reaction (60%), and cortical and medullary inflammation (95% and 75%, respectively). Medullary inflammation, giant cell reaction, and the extent of cast formation correlated with eGFR value at LCCN diagnosis. During a median follow-up of 22 months, mean eGFR increased to 43 ± 30 mL/min/1.73 m2. Age, β2-microglobulin, best hematologic response, number of cortical casts per square millimeter, and degree of interstitial fibrosis/tubular atrophy (IFTA) were independently associated with a higher eGFR during follow-up. This eGFR value correlated with overall survival, independently of the hematologic response. This study shows that extent of cast formation and IFTA in LCCN predicts the quality of renal response, which, in turn, is associated with overall survival.

The effects of lithium treatment on renal function have been previously shown, albeit with discrepancies regarding their relevance. In this study, we examined glomerular filtration rate in patients treated with lithium for up to 33 years. All lithium patients registered from 1980 to 2012 at a Lithium Clinic were screened. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine concentration using the Modification of Diet in Renal Disease Study Group equation. A cross-sectional evaluation of the last available eGFR of 953 patients was carried out using multivariate regression analysis for gender, current age, and duration of lithium treatment. Survival analysis was subsequently applied to calculate the time on lithium needed to enter the eGFR ranges 45 to 59 mL/min/1.73 m2 (G3a) or 30 to 44 mL/min/1.73 m2 (G3b). Finally, 4-year follow-up of eGFR was examined in subgroups of patients who, after reduction to an eGFR lower than 45 mL/min/1.73 m2 either i) continued lithium at the same therapeutic range or ii) discontinued lithium or continued at concentrations below the therapeutic range (0.5 mmol/L). In the cross-sectional evaluation, eGFR was found to be lower in women (by 3.47 mL/min/1.73 m2), in older patients (0.73 mL/min/1.73 m2 per year of age), and in patients with longer lithium treatment (0.73 mL/min/1.73 m2 per year). Half of the patients treated for longer than 20 years had an eGFR lower than 60 mL/min/1.73 m2. The median time on lithium taken to enter G3a or G3b was 25 years (95% CI, 23.2–26.9) and 31 years (95% CI, 26.6–35.4), respectively. Progression of renal failure throughout the 4-year follow-up after a reduction to an eGFR lower than 45 mL/min/1.73 m2 did not differ between the subgroup who continued lithium as before and the subgroup who either discontinued lithium or continued at concentrations below the therapeutic range. Duration of lithium treatment is to be added to advancing age as a risk factor for reduced glomerular filtration rate. However, renal dysfunction tends to appear after decades of treatment and to progress slowly and irrespective of lithium continuation.

Onconephrology is an emerging medical subspecialty focused on the numerous interconnections between cancer and kidney diseases. Patient with malignancies commonly experience kidney problems including acute kidney injury, tumor lysis syndrome, fluid and electrolyte disorders and chronic kidney disease, often as a consequence of the anti-cancer treatment. Conversely, a number of glomerulopathies, tubulopathies and vascular renal diseases can early signal the presence of an underlying cancer. Furthermore, the administration of immunosuppressive drugs, especially cytotoxic drugs and calcineurin inhibitors, may strongly impair the immune response increasing the risk of cancer. The objective of this review article is to: (i) discuss paraneoplastic glomerular disease, (ii) review cancer as an adverse effect of immunosuppressive agents used to treat glomerulopathies, and (iii) in the absence of international approved guidelines, propose a screening program based on expert opinion aimed at guiding nephrologists to early detect malignancies during their clinical practice.

The adverse renal effects of lithium have long been known, but glomerular insufficiency had been considered an unlikely event until recently, when new studies have raised concern regarding very long-term treatment. In this cross-sectional study, we examined glomerular function in a cohort of patients treated with lithium for up to 33 years and a control group of lithium-naïve patients treated with other mood-stabilizers.

Background: The relationship of kidney size to ageing, kidney function and kidney disease risk factors is not fully understood.Methods: Ultrasound length and parenchymal kidney volume were determined from a population-based sample of 3972 Sardinians (age range 18–100 years). We then identified the subset of 2256 ‘healthy’ subjects to define age- and sex-specific reference ranges (2.5–97.5 percentile) of kidney volume. Logistic regression (accounting for family clustering) was used to identify the clinical characteristics associated with abnormally large kidneys or abnormally small kidneys.Results: In the healthy subset, kidney volume and length increased up to the fourth to fifth decade of life followed by a progressive decrease in men, whereas there was a gradual kidney volume decrease throughout the lifespan of women. In the whole sample, independent predictors of lower kidney volume (97.5 percentile for age and sex) were younger age, female sex, diabetes, obesity, high height, high waist:hip ratio and lower SCr. Estimated heritability for kidney volume was 15%, and for length 27%; kidney volume correlated strongly with birthweight.Conclusions: Overall, in a general healthy population, kidney measures declined with age differently in men and women. The determinants of kidney parenchymal volume include genetic factors and modifiable clinical factors.

The prevalence of CKD and of renal failure vary worldwide, yet parallel increases in leading risk factors explain only part of the differential prevalence. We measured CKD prevalence and eGFR, and their relationship with traditional and additional risk factors, in a Sardinian founder population cohort. The eGFR was calculated using equations from the CKD Epidemiology Collaboration and Modification of Diet in Renal Disease studies. With use of the Kidney Disease Improving Global Outcomes guidelines, a cross-sectional analysis of 4842 individuals showed that CKD prevalence was 15.1%, including 3.6% of patients in the high-risk and 0.46% in the very-high-risk categories. Longitudinal analyses performed on 4074 of these individuals who completed three visits with an average follow-up of 7 years revealed that, consistent with other populations, average eGFR slope was -0.79 ml/min per 1.73 m(2) per year, but 11.4% of the participants had an eGFR decline >2.3 ml/min per 1.73 m(2) per year (fast decline). A genetic score was generated from 13 reported eGFR- and CKD-related loci, and univariable and multivariable analyses were applied to assess the relationship between clinical, ultrasonographic, and genetic variables with three outcomes: CKD, change in eGFR, and fast eGFR decline. Genetic risk score, older age, and female sex independently correlated with each outcome. Diabetes was associated with CKD prevalence, whereas hypertension and hyperuricemia correlated more strongly with fast eGFR decline. Diabetes, hypertension, hyperuricemia, and high baseline eGFR were associated with a decline of eGFR. Along with differential health practices, population variations in this spectrum of risk factors probably contributes to the variable CKD prevalence worldwide.