Use of tocilizumab in kidney transplant recipients with COVID-19.

Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin-6 (IL-6) release. The IL-6-receptor blocker tocilizumab may control the aberrant host immune response in patients with coronavirus disease 2019 (COVID-19) . In this pandemic, kidney transplant (KT) recipients are a high-risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID-19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (hazard ratio [HR] 3.12 for those older than 60 years, P = .039). IL-6 and other inflammatory markers, including lactic acid dehydrogenase, ferritin, and D-dimer increased early after tocilizumab administration and their values were higher in nonsurvivors. Instead, C-reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in nonsurvivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [confidence interval 1.004-1.024], P = .003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration and did not have an impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID-19 but randomized trials are needed.

Helicobacter pylori pathogenicity and primary antimicrobial resistance in Northern Spain.

BACKGROUND: Helicobacter pylori infection is associated with chronic gastritis, ulcers and gastric cancer. Antimicrobial resistance has increased worldwide affecting the efficacy of current treatments. Most guidelines recommend implementation of regional surveillance of primary antibiotic resistance of H pylori. Only a fraction of individuals infected with H pylori develop gastric diseases which are related to virulence factors of the bacteria. The aims of the study were to determine the primary antimicrobial resistance rates of H pylori and to know the virulence factors prevalence of strains circulating in Southern Europe. MATERIALS AND METHODS: Susceptibility testing by Etest to clarithromycin, levofloxacin, metronidazole, amoxicillin and tetracycline was performed in 102 isolates (99 naïve patients). The prevalence of virulence factors (cagA, vacA, oipA, babA and dupA) was evaluated in 102 H pylori isolates from patients with mild-disease symptoms and in 22 isolates from patients with severe-disease symptoms. RESULTS: Primary resistance rates were 12.1% to clarithromycin, 13.1% to levofloxacin, 24.2% to metronidazole and 0% to amoxicillin and tetracycline. Combined resistance to clarithromycin and levofloxacin was 3% and to clarithromycin and metronidazole 4%. Prevalence of virulence factors in the mild- and severe-disease group was 35.3% and 81.8% for cagA, 20.6% and 54.5% for cagA/vacAs1m1, 94.1% and 95.4% for babA2, 78.4% and 100% for oipA and 30.4% and 18.2% for dupA. CONCLUSIONS: Primary antimicrobial resistance rates were under 15% for clarithromycin and levofloxacin. The prevalence of H pylori carrying the virulent genotype cagA/vacAs1m1 was higher than 20% in the mild-disease and 54% in the severe-disease symptom group.

Antimicrobial Susceptibility-Guided Therapy Versus Empirical Concomitant Therapy for Eradication of Helicobacter pylori in a Region with High Rate of Clarithromycin Resistance.

BACKGROUND: Nonbismuth quadruple (concomitant) regimen is recommended for first-line empirical Helicobacter pylori (HP) eradication treatment when clarithromycin resistance is more than 15-20%. Our objective was to evaluate the efficacy and tolerability of concomitant versus antimicrobial susceptibility-guided treatment in an area with high rates of clarithromycin resistance. METHODS: Three hundred consecutive HP-infected patients received antimicrobial susceptibility-guided therapy or empirical concomitant therapy for 10 days. The concomitant regimen was omeprazole (20 mg/12 hour), amoxicillin (1 g/12 hour), clarithromycin (500 mg/12 hour), and metronidazole (500 mg/12 hour) (OACM). Patients diagnosed by culture received one of three combinations of antibiotics based on susceptibility results: omeprazole, amoxicillin, and clarithromycin (OAC); omeprazole, amoxicillin, and levofloxacin (OAL); or omeprazole, amoxicillin, and metronidazole (OAM), at the aforementioned doses (and 500 mg/12 hour in the case of levofloxacin). Eradication was confirmed with a (13)C urea breath test, 6 weeks after treatment. Adverse events and adherence were assessed with questionnaires and reviewing medication sachets. RESULTS: The mean age was 50 years, 59% were women, and 14% had peptic ulcers. Concomitant and antimicrobial susceptibility-guided eradication rates were, respectively, 87% and 94% by intention-to-treat (p = .08) and 89% and 95% (p = .08) per protocol per-protocol analysis. Adverse effects were reported in 31% of patients on OACM and 15% of those on susceptibility-guided therapy (p < .05). CONCLUSIONS: For HP eradication in a region with high rates of multiple drug resistance, antimicrobial susceptibility-guided therapy is more effective than empirical concomitant therapy.

Helicobacter pylori Infection in Children. Antimicrobial Resistance and Treatment Response.

BACKGROUND: The aim of this study was to determine the appropriateness of the recent recommendations for managing Helicobacter pylori infection in children in a university hospital in Southern Europe. Antimicrobial resistance and response to eradication therapy were also determined. MATERIALS AND METHODS: The presence of H. pylori was studied in 143 children: by gastric biopsy culture (GBC), (13)C-urea breath test (UBT) and stool antigen immunochromatography test (SAIT) in 56 children; by GBC and UBT in 20, by GBC and SAIT in 18, and by GBC alone in 49. Antimicrobial susceptibility was determined by E-test. Infection was defined as a positive culture or positivity in both UBT and SAIT. Disease progression was studied in 118 patients. First evaluation of symptoms was carried out at 3-6 months after diagnosis and/or after treatment of the infection. RESULTS: H. pylori was detected in 74 from the 143 children analyzed (100% GBC positive, 98.1% UBT positive, and 58.1% SAIT positive). The main symptom was chronic abdominal pain (n = 121). Macroscopic antral nodularity was observed in 29.7% of infected patients and in 5.8% of uninfected patients, respectively. Resistance to clarithromycin and metronidazole was found in 34.7 and 16.7%, respectively. Eradication when susceptible antimicrobials were used occurred in 78.7% (48/61) versus 37.5% (3/8) when the treatment included a drug with resistance (p = .024). In patients with recurrent abdominal pain, symptoms resolved in 92.9% (39/42) patients with HP eradication versus 42.9% (6/14) without HP eradication (p < .001). CONCLUSION: Treated patients often failed to meet the criteria established in the guidelines for H. pylori diagnostic screening and treatment because most of them had only recurrent abdominal pain, but remission of their symptoms was associated with H. pylori eradication.

High rate of fecal carriage of extended-spectrum-ß-lactamase-producing Escherichia coli in healthy children in Gipuzkoa, northern Spain.

The prevalence of extended-spectrum-ß-lactamase-producing Enterobacteriaceae (ESBLPE) was studied in stool samples from 125 8- to 16-month-old healthy children. Twenty-four percent of them and 10.7% of the 318 fecal samples studied yielded extended-spectrum-ß-lactamase-producing Escherichia coli, with the types being SHV-12, CTX-M-1, CTX-M-14, and TEM-52, the most common types of ß-lactamases. This high prevalence of ESBLPE in healthy people, which is to our knowledge the highest currently reported in Europe, may represent a risk for increased infections by these organisms in the future.

The role of copeptin in kidney disease.

Copeptin is a 39-amino acid glycopeptide that is secreted equimolecularly with arginine-vasopressin (AVP) from the prepro-hormone AVP in the posterior pituitary. While AVP is a very unstable molecule and is accompanied by significant technical troubles in its quantification, copeptin is a stable and easily quantifiable molecule. For this reason, circulating copeptin is currently used as a surrogate for AVP in different pathological conditions, including renal diseases. In recent years it has been shown that copeptin is associated with an increased risk of developing chronic kidney disease in the general population. In addition, copeptin has also been associated with multiple renal diseases with relevant clinical consequences and potential therapeutic implications. In the present review, we update and summarize the clinical significance of copeptin as a surrogate marker for AVP concentrations in different kidney diseases, as well as in renal replacement therapy (hemodialysis and peritoneal dialysis) and renal transplantation.

Effect of Immunosuppressive Treatments on Kidney Outcomes After Gross Hematuria-Related Acute Kidney Injury in Older Patients With IgA Nephropathy.

Introduction: Macroscopic hematuria (MH) bouts, frequently accompanied by acute kidney injury (AKI-MH) are one of the most common presentations of IgA nephropathy (IgAN) in the elderly. Immunosuppressive therapies are used in clinical practice; however, no studies have analyzed their efficacy on kidney outcomes. Methods: This is a retrospective, multicenter study of a cohort of patients aged ≥50 years with biopsy-proven IgAN presenting with AKI-MH. Outcomes were complete, partial, or no recovery of kidney function at 1 year after AKI-MH, and kidney survival at 1, 2, and 5 years. Propensity score matching (PSM) analysis was applied to balance baseline differences between patients treated with immunosuppression and those not treated with immunosuppression. Results: The study group consisted of 91 patients with a mean age of 65 ± 15 years, with a mean follow-up of 59 ± 36 months. Intratubular red blood cell (RBC) casts and acute tubular necrosis were found in all kidney biopsies. The frequency of endocapillary hypercellularity and crescents were low. Immunosuppressive therapies (corticosteroids alone or combined with mycophenolate mofetil or cyclophosphamide) were prescribed in 52 (57%) patients, whereas 39 (43%) received conservative treatment. There were no significant differences in the proportion of patients with complete, partial, or no recovery of kidney function at 1 year between patients treated with immunosuppression and those not treated with immunosuppression (29% vs. 36%, 30.8% vs. 20.5% and 40.4 % vs. 43.6%, respectively). Kidney survival at 1, 3, and 5 years was similar among treated and untreated patients (85% vs. 81%, 77% vs. 76% and 72% vs. 66%, respectively). Despite the PSM analysis, no significant differences were observed in kidney survival between the two groups. Fourteen patients (27%) treated with immunosuppression had serious adverse events. Conclusions: Immunosuppressive treatments do not modify the unfavorable prognosis of patients with IgAN who are aged ≥50 years presenting with AKI-MH, and are frequently associated with severe complications.

Enhanced leishmanicidal activity of cryptopeptide chimeras from the active N1 domain of bovine lactoferrin.

Two antimicrobial cryptopeptides from the N1 domain of bovine lactoferrin, lactoferricin (LFcin17-30) and lactoferrampin (LFampin265-284), together with a hybrid version (LFchimera), were tested against the protozoan parasite Leishmania. All peptides were leishmanicidal against Leishmania donovani promastigotes, and LFchimera showed a significantly higher activity over its two composing moieties. Besides, it was the only peptide active on Leishmania pifanoi axenic amastigotes, already showing activity below 10 µM. To investigate their leishmanicidal mechanism, promastigote membrane permeabilization was assessed by decrease of free ATP levels in living parasites, entrance of the vital dye SYTOX Green (MW = 600 Da) and confocal and transmission electron microscopy. The peptides induced plasma membrane permeabilization and bioenergetic collapse of the parasites. To further clarify the structural traits underlying the increased leishmanicidal activity of LFchimera, the activity of several analogues was assessed. Results revealed that the high activity of these hybrid peptides seems to be related to the order and sequence orientation of the two cryptopeptide moieties, rather than to their particular linkage through an additional lysine, as in the initial LFchimera. The incorporation of both antimicrobial cryptopeptide motifs into a single linear sequence facilitates chemical synthesis and should help in the potential clinical application of these optimized analogues.

Impaired virulence and in vivo fitness of colistin-resistant Acinetobacter baumannii.

Acinetobacter baumannii (American Type Culture Collection strain 19606) acquires mutations in the pmrB gene during the in vitro development of resistance to colistin. The colistin-resistant strain has lower affinity for colistin, reduced in vivo fitness (competition index, .016), and decreased virulence, both in terms of mortality (0% lethal dose, 6.9 vs 4.9 log colony-forming units) and survival in a mouse model of peritoneal sepsis. These results may explain the low incidence and dissemination of colistin resistance in A. baumannii in clinical settings.

Essential Role of Enzymatic Activity in the Leishmanicidal Mechanism of the Eosinophil Cationic Protein (RNase 3).

The recruitment of eosinophils into Leishmania lesions is frequently associated with a favorable evolution. A feasible effector for this process is eosinophil cationic protein (ECP, RNase 3), one of the main human eosinophil granule proteins, endowed with a broad spectrum of antimicrobial activity, including parasites. ECP was active on Leishmania promastigotes and axenic amastigotes (LC50's = 3 and 16 µM, respectively) but, in contrast to the irreversible membrane damage caused on bacteria and reproduced by its N-terminal peptides, it only induced a mild and transient plasma membrane destabilization on Leishmania donovani promastigotes. To assess the contribution of RNase activity to the overall leishmanicidal activity of ECP, parasites were challenged in parallel with a single-mutant version, ECP-H15A, devoid of RNase activity, that fully preserves the conformation and liposome permeabilization ability. ECP-H15A showed a similar uptake to ECP on promastigotes, but with higher LC50's (>25 µM) for both parasite stages. ECP-treated promastigotes showed a degraded RNA pattern, absent in ECP-H15A-treated samples. Moreover ECP, but not ECP-H15A, reduced more than 2-fold the parasite burden of infected macrophages. Altogether, our results suggest that ECP enters the Leishmania cytoplasm by an endocytic pathway, ultimately leading to RNA degradation as a key contribution to the leishmanicidal mechanism. Thus, ECP combines both membrane destabilization and enzymatic activities to effect parasite killing. Taken together, our data highlight the microbicidal versatility of ECP as an innate immunity component and support the development of cell-penetrating RNases as putative leishmanicidal agents.

Structural framework for the modulation of the activity of the hybrid antibiotic peptide cecropin A-melittin [CA(1-7)M(2-9)] by Nε-lysine trimethylation.

The 3D structures of six linear pentadecapeptides derived from the cecropin A-melittin antimicrobial peptide CA(1-7)M(2-9) [KWKLFKKIGAVLKVL-NH(2)] have been studied. These analogues are modified by ε-NH(2) trimethylation of one or more lysine residues and showed variation in both antimicrobial and cytotoxic activities, depending on the number and position of modified lysines. Since it is expected that these peptides will display a strong conformational ordering when in contact with membranes, we have investigated their structure on the basis of the data extracted from NMR experiments performed in membrane-mimetic environments. We show that inclusion of N(ε)-trimethylated lysine residues induces a certain degree of structural flexibility, while preserving to a variable extent a largely α-helical structure. In addition, peptide orientation with respect to SDS micelles has been explored by detection of the intensity changes of peptide NMR signals upon addition of a paramagnetic probe (Mn(2+) ions).

Acute responses of gastrointestinal hormones to both oral and parenteral intradialytic nutrition.

INTRODUCTION: Intradialytic nutrition (IDN) has been used to improve the nutritional status of malnourished hemodialysis (HD) patients. OBJECTIVE: To evaluate the different effects of parenteral IDN (IDPN) and oral IDN (IDON) on nutrition-related gastrointestinal hormones. PATIENTS AND METHODS: Seven clinically stable HD patients with malnutrition were included. All patients were treated for 1 month with either IDPN or IDON, with a 4-week period of no nutritional support between each type of therapy. On the first day of each nutritional support (IDON or IDPN) we analyzed the acute responses of insulin, ghrelin, and glucagon-like peptide 1 (GLP-1). We compared the areas under the secretory curves (AUC) and the maximum peaks of serum glucose, insulin, ghrelin, and GLP-1. A group of 6 clinically stable HD patients without any type of IDN served as the control group. RESULTS: The acute responses of glucose and insulin to IDN were significantly higher with IDPN than with IDON. The AUC of glucose (602 ± 81 vs. 495 ± 81 mg/dl/h, p < 0.01) and insulin (232 ± 103 vs. 73.8 ± 69 µU/ml/h, p < 0.01) as well as the maximum peaks of glucose (228 ± 41 vs. 177 ± 47 mg/dl, p < 0.05) and insulin (104 ± 46 vs. 29 ± 24 µU/ml, p < 0.01) were significantly higher after IDPN than after IDON. Ghrelin decreased after both IDPN and IDON; however, the decrease was significantly higher with IDPN compared to IDON. The ghrelin nadir was significantly lower in IDPN than in IDON (0.77 ± 0.5 vs. 1.5 ± 0.3, p < 0.05) although the AUC of ghrelin was not significantly different. GLP-1 was significantly increased at 1 h after starting both IDPN and IDON with no significant differences between the groups. CONCLUSION: IDPN induces a higher increase in serum glucose and insulin levels and a greater reduction in serum ghrelin concentrations compared with an equivalent orally administered nutritional supplement.

[Renal biopsy in patients aged 65 years or older: are there differences in the indication and histopathology compared to other patients?]. / La biopsia renal en pacientes de 65 o más años: ¿existen diferencias en la indicación y en la histopatología respecto al resto de pacientes?

BACKGROUND: Renal biopsy (RB) represents the gold standard for diagnosis of kidney diseases. In this paper we analyse whether the indication of RB and histopathology in patients 65 years or older is different from the other patients. MATERIAL AND METHODS: Retrospective study of 93 native renal biopsies performed in the General Hospital of Segovia in the period 2004-2008. The RB was performed percutaneously under ultrasound guidance in real time, using a 16G automatic needle. RESULTS: Mean age of biopsied patients was 56.89 ± 19 (range 14-89) , and 57% were males. A total of 39RB were performed on people aged 65 years or older. Overall, nephrotic syndrome (NS) is the most common indication of RB, and IgA glomerulonephritis the most common histology. In people ≥ 65 years, acute renal failure (ARF) is the most common indication for RB, and rapidly progressing (crescentic) glomerulonephritis/vasculitis the most detected the diagnosis. When taking age into account, no significant differences in the number of glomeruli obtained by RB or in the number of RB performed on the same patient. CONCLUSIONS: In people 65 years or older, ARF is the main indication of RB and crescentic glomerulonephritis/vasculitis the most frequent diagnosis.

[Estimation of glomerular filtration rate in persons aged 69 years or older: agreement between distinct calculation methods]. / Estimación del filtrado glomerular en personas de 69 años o más: concordancia entre diferentes métodos de cálculo.

MATERIAL: Estimation of glomerular filtration rate (eGFR) is the most widely accepted marker of renal function. Precise calculation is not routinely performed in clinical practice. Several methods have been developed for eGFR: creatinine clearance (CCr) calculation or the use of formulae derived from serum creatinine (sCr). The present study aimed to analyze the agreement between distinct methods of calculating eGFR. MATERIAL AND METHODS: We performed a cross-sectional study between January and April, 2006 in 32 stable elders, aged 69 years or older, evaluated in a general nephrology unit. eGFR was calculated by CCr (considered the gold standard), Cockcroft-Gault (CG) and Modification of Renal Diet in Disease (MDRD) equations. The Mann Whitney U-test, Spearman's correlation coefficient and the Kappa coefficient were used to compare means and determine the concordance between methods. RESULTS: The overall means+/-SD of GFRe for CCr were 36.14+/-16 ml/min (range 11.75-69.6); CG: 37.02+/-16 ml/min (range 13.3-72.3) and MDRD: 45.52+/-16 ml/min (range 19.2-75.36). Variations in eGFR on comparison of methods were CCr and MDRD: -9.37 ml/min (95% CI:-13.85, -4.9); CCr and CG:-2.54 ml/min (95% CI: -6.95, 1.80); MDRD and CG: 9.0 ml/min (95% CI: 5.96, 12). The correlation between the gold standard (CCr) and sCr-derived formulae was r=0.74 for MDRD (P<0.001) and r=0.77 for CG (P<0.001). The Kappa value for CCr and CG was 0.44 and was 0.35 for CCr and MDRD. When patients were classified by stage of chronic renal disease, discrepancies were found according to the method used: stage 5 (eGFR<15 ml/min) was diagnosed in 13.63% with CG while none were diagnosed with stage 5 with MDRD. CONCLUSIONS: In the estimation of the renal function in the elderly, eGFRe levels can differ in the same patient according to the method used: in view of the degree of concordance between CG and CCr, this mathematical formula should be used in preference to MDRD.

The cost of resistance to colistin in Acinetobacter baumannii: a proteomic perspective.

Colistin resistance in Acinetobacter baumannii, a pathogen of clinical concern, was induced in the susceptible strain ATCC 19606 by growth under increasing pressure of the antibiotic, the only drug universally active against multi-resistant clinical strains. In 2-D difference gel electrophoresis (DIGE) experiments, 35 proteins with differences in expression between both phenotypes were identified, most of them appearing as down regulated in the colistin-resistant strain. These include outer membrane (OM) proteins, chaperones, protein biosynthesis factors, and metabolic enzymes, all suggesting substantial loss of biological fitness in the resistant phenotype, as substantiated by complementary experiments in the absence of colistin. Results shed light on the scarcity of widespread clinical outbreaks for resistant phenotypes.

High stable serum adiponectin levels are associated with a better outcome in prevalent dialysis patients.

AIMS: Our aim was to evaluate the prognostic value of 2 measurements of serum adiponectin levels for all-cause mortality and cardiovascular (CV) mortality in uremic patients. METHODS: We analyzed 184 patients (19-86 years) undergoing peritoneal dialysis (n = 86) or hemodialysis (n = 98). All patients had 2 measurements of serum adiponectin levels (at baseline and after 1 year). Relationships between adiponectin and mortality were studied by means of survival analysis and Cox regression analysis. RESULTS: During a median follow-up time of 31.2 months, 67 patients (36.4%) died, 26 (14.1%) as a result of CV disease. Mean survival time for CV mortality in patients with 1-year adiponectin values in the upper tertile was significantly higher than that found in patients in the middle and lower tertiles. Hazard ratios (HR) for all-cause mortality per SD change were 0.70 (95% CI, 0.50-0.98; p < 0.05) for baseline adiponectin levels and 0.68 (0.49-0.95; p < 0.05) for mean baseline and 1-year adiponectin levels. Mean adiponectin levels were also negatively related with CV mortality [HR 0.43 (0.21-0.86); p < 0.05] and CV events [HR 0.74 (0.55-0.99); p < 0.05]. CONCLUSIONS: In this population of dialysis patients, adiponectin seems to behave as a CV protective factor. Patients with high mean adiponectin levels had a better survival rate.

[Laboratory manifestations associated with chronic renal failure: what degree of estimated glomerular filtration can be used for its detection in the elderly?]. / Las manifestaciones analíticas asociadas a la insuficiencia renal crónica: ¿a partir de qué grado de filtrado glomerular estimado las detectamos en ancianos?

OBJECTIVE: A classification of chronic kidney disease (CKD) based on stages of glomerular filtration (GF) has recently been developed. Thus, chronic renal failure (CRF) is based on GF <60 ml/min. Our goal was to study the presence of typical manifestations of CRF in elderly individuals with a GF of <60 ml/min (stage 3-5) and to determine the cut-off value at which GF can be used to detect these manifestations. MATERIAL AND METHODS: We performed a cross-sectional study in clinically-stable elderly patients attending the geriatrics and nephrology outpatient department. The estimated GF (GFe) was established with the Cockroft-Gault and abbreviated Modification of Diet in Renal Disease Study (MDRD) formulae. Because these patients had a GF of less than 60 ml/min, they were expected to show the manifestations associated with CRF (anaemia, metabolic acidosis, abnormal bone and mineral metabolism). We evaluated the occurrence of these manifestations and the GF cut-off at which they were detected. To do this, the population was divided into two groups: group A: patients with GFe > or = 30 ml/min (stage 3, N=48); and group B: patients with GFe <30 ml/min (stages 4-5, N=8). RESULTS: Seventy percent of the patients had a GFe (MDRD) <60 ml/min (stage 3-5). Despite reduced GF, these patients did not show the typical manifestations of CRF. Group B showed higher plasmatic levels of creatinine, urea, uric acid, and potassium and required treatment with erythropoietin and calcium salts. CONCLUSIONS: Many elderly people diagnosed with CKD with the current classification do not show manifestations of CRF. Estimation of the GF in elders should be generalized to correctly adjust medication to renal impairment rather than to classify elders into CKD stage.

IgA Nephropathy in Elderly Patients.

BACKGROUND AND OBJECTIVES: Some studies suggest that the incidence of IgA nephropathy is increasing in older adults, but there is a lack of information about the epidemiology and behavior of the disease in that age group. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this retrospective multicentric study, we analyzed the incidence, forms of presentation, clinical and histologic characteristics, treatments received, and outcomes in a cohort of 151 patients ≥65 years old with biopsy-proven IgA nephropathy diagnosed between 1990 and 2015. The main outcome was a composite end point of kidney replacement therapy or death before kidney replacement therapy. RESULTS: We found a significant increase in the diagnosis of IgA nephropathy over time from six patients in 1990-1995 to 62 in 2011-2015 (P value for trend =0.03). After asymptomatic urinary abnormalities (84 patients; 55%), AKI was the most common form of presentation (61 patients; 40%). Within the latter, 53 (86%) patients presented with hematuria-related AKI (gross hematuria and tubular necrosis associated with erythrocyte casts as the most important lesions in kidney biopsy), and eight patients presented with crescentic IgA nephropathy. Six (4%) patients presented with nephrotic syndrome. Among hematuria-related AKI, 18 (34%) patients were receiving oral anticoagulants, and this proportion rose to 42% among the 34 patients older than 72 years old who presented with hematuria-related AKI. For the whole cohort, survival rates without the composite end point were 74%, 48%, and 26% at 1, 2, and 5 years, respectively. Age, serum creatinine at presentation, and the degree of interstitial fibrosis in kidney biopsy were risk factors significantly associated with the outcome, whereas treatment with renin-angiotensin-aldosterone blockers was associated with a lower risk. Immunosuppressive treatments were not significantly associated with the outcome. CONCLUSIONS: The diagnosis of IgA nephropathy among older adults in Spain has progressively increased in recent years, and anticoagulant therapy may be partially responsible for this trend. Prognosis was poor. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_07_16_CJASNPodcast_19_08_.mp3.

Nephrotic-range proteinuria in a patient with a giant prolactinoma.

We report for the first time a case of nephrotic-range proteinuria adequately controlled by using dopamine agonists. A 40-year-old man was studied because of persistent asymptomatic nephrotic proteinuria despite lifestyle modifications and treatment with converting enzyme inhibitors. The renal biopsy specimen did not show histopathologic changes. In the follow-up period, a giant prolactinoma was found by chance with extremely high prolactin (PRL) values. After establishing cabergoline therapy, we achieved a remarkable decrease in both serum PRL levels and tumor mass, and surprisingly, proteinuria disappeared. We discuss the possible pathogenic mechanisms of proteinuria that may correspond to PRL level in urine (prolactinuria) or another tumor-related protein.

Nephrotic syndrome resulting from focal segmental glomerulosclerosis in a peripheral blood stem cell transplant patient.

We describe the case of a male patient who was diagnosed with acute monoblastic leukemia and received a peripheral stem cell transplantation (PSCT) with peripheral blood hematopoietic progenitors. Because he was in clinical remission with no evidence of chronic graft-versus-host disease (GVHD), immunosuppression was withdrawn, and he developed nephrotic syndrome (NS) months later. A kidney biopsy showed focal segmental glomerulosclerosis (FSGS) as part of the GVHD. Soon after the reintroduction of previous immunosuppressive therapy, we observed a complete remission of the NS.