Renal involvement in sarcoidosis: histological patterns and prognosis, an Italian survey.

BACKGROUND: Granulomatous interstitial nephritis in sarcoidosis (sGIN) is generally clinically silent, but in <1% causes acute kidney injury (AKI). METHODS: This Italian multicentric retrospective study included 39 sarcoidosis-patients with renal involvement at renal biopsy: 31 sGIN-AKI, 5 with other patterns (No-sGIN-AKI), 3 with nephrotic proteinuria. We investigate the predictive value of clinical features, laboratory, radiological parameters and histological patterns regarding steroid response. Primary endpoint: incident chronic kidney disease (CKD) beyond the 1°follow-up (FU) year; secondary endpoint: response at 1°line steroid therapy; combined endpoint: the association of initial steroid response and outcome at the end of FU. RESULTS: Complete recovery in all 5 No-sGIN-AKI-patients, only in 45% (13/29) sGIN-AKI-patients (p=0.046) (one lost in follow-up, for another not available renal function after steroids). Nobody had not response. Primary endpoint of 22 sGIN-AKI subjects: 65% (13/20) starting with normal renal function developed CKD (2/22 had basal CKD; median FU 77 months, 15-300). Combined endpoint: 29% (6/21) had complete recovery and final normal renal function (one with renal relapse), 48% (10/21) had partial recovery and final CKD (3 with renal relapse, of whom one with basal CKD) (p=0.024). Acute onset and hypercalcaemia were associated to milder AKI and better recovery than subacute onset and patients without hypercalcaemia, women had better endpoints than men. Giant cells, severe interstitial infiltrate and interstitial fibrosis seemed negative predictors in terms of endpoints. CONCLUSIONS: sGIN-AKI-patients with no complete recovery at 1°line steroid should be treated with other immunosuppressive to avoid CKD, in particular if males with subacute onset and III stage-not hypercalcaemic AKI.

Cardiovascular morbidity and long term mortality associated with in hospital small increases of serum creatinine.

BACKGROUND: The cardiovascular risk associated with an increase in serum creatinine below the acute kidney injury (AKI) threshold, during hospitalization, has not been studied in depth. We assessed patients' features and outcomes associated with these changes. METHODS: Retrospective cohort study of 12,493 consecutive patients admitted to hospital throughout 12 months. We investigated the patients who had a small creatinine increase (SISCr) between 1.2 and <1.5 times the admission value, and tested the association of creatinine changes with the prevalence of cardiovascular disease (CVD). In a follow-up study, we assessed the all-cause mortality and its relationship with SISCr. RESULTS: Among patients with two or more creatinine measurements, 14.9% showed a SISCr. Older age, female gender and higher estimated glomerular filtration rate (eGFR) at admission were characteristics of these patients. The prevalence of CVD was 14.6% in patients with SISCr vs. 10.7% in those with stable creatinine (p < 0.001). SISCr was detected in 36, 26.6 and 18.9% of chronic heart failure (CHF), chronic ischemic heart disease (CIHD) and acute myocardial infarction (AMI) patients, respectively. The follow-up was 26.7 ± 10.6 months with 770 all-cause deaths. Serum creatinine increase above 20% was associated with a significant higher mortality compared to changes below 20%, adjusted hazard (HR) ratio 1.577 (p < 0.001). A higher risk was found associated with creatinine increases >1.5 times the baseline: HR 1.704 (p < 0.001). CONCLUSIONS: In hospitalized patients, increases in serum creatinine below the AKI threshold are associated with CHF, CIHD and long-term mortality.

WITHDRAWN: Nephrotic syndrome in primary myelofibrosis with renal extramedullary hematopoiesis and glomerulopathy in the JAK inhibitor era.

Ahead of Print article withdrawn by publisher. The publisher apologizes for any inconvenience this has caused. The article was scheduled for the journal "Clinical Nephrology. Case Studies" (issn 2196-5293). The article is available in PubmedCentral: https://www.ncbi.nlm.nih.gov/pubmed/29350220 
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Nephrotic syndrome in primary myelofibrosis with renal extramedullary hematopoiesis and glomerulopathy in the JAK inhibitor era.

Primary myelofibrosis (PMF) is an uncommon form of myeloproliferative neoplasm (MPN) characterized by a proliferation of predominantly megakaryocytes and granulocytes in the bone marrow that, in fully-developed disease, is associated with reactive deposition of fibrous connective tissue, extramedullary hematopoiesis (EMH), and splenomegaly. Kidney involvement is rare and clinically presents with proteinuria, nephrotic syndrome, and renal insufficiency. Renal damage can be due to EMH and glomerulopathy. Renal EMH presents three patterns: infiltration of the interstitium with possible renal failure caused by functional damage of parenchyma and vessels, infiltration of capsule and pericapsular adipose tissue, and sclerosing mass-like lesions that can cause hydronephrosis and hydroureter with obstructive uropathy and renal failure. Glomerulopathy associated with PMF is rarely described, ranging from 1 month to 18 years from diagnosis of the neoplasm to renal biopsy. It is characterized by expansion and hypercellularity mesangial, segmental sclerosis, features of chronic thrombotic microangiopathy (TMA), and intracapillary hematopoietic cells infiltrating in absence of immune-mediated glomerulonephritis. We present a nephrotic syndrome in PMF-related glomerulopathy, associated with EMH, without renal failure, in a patient under treatment for 2 years with JAK2 inhibitor ruxolitinib. Despite treatment, the patient died 7 months after renal biopsy. Nephrologists still know very little about this topic and there is no homogeneous data about incidence, pathogenesis, and optimal treatment of this poor prognostic PMF-associated nephrotic syndrome. We focus on data in the literature in the hope of stimulating hematologists, nephrologists, pathologists to future studies about the natural history of renal involvement, useful for optimal management of this rare pathology.

Increased acid excretion in kidney stone formers with essential hypertension.

BACKGROUND: Although several studies have reported that kidney stone disease and hypertension are associated, the link between the two conditions has not been identified. This study investigated urinary excretion of different solutes, particularly citrate and acids, in kidney stone formers and examined their association with high blood pressure. METHODS: The retrospective study included 234 consecutive subjects, aged 47.0 +/- 15.6, attending our metabolic clinic after episodes of kidney stones. Essential hypertension was present in 82 patients (35.0%). A difference in the urinary excretion of some of the investigated components was found between subjects with normal blood pressure and those with hypertension. RESULTS: The results showed that hypertensive subjects were older and had a higher body mass index (BMI) and serum uric acid. They had a significantly lower urinary pH (5.6 +/- 0.4 versus 6.0 +/- 0.5) and citrate (2.55 +/- 1.36 versus 2.83 +/- 1.65 mmol/24 h), higher titratable acid (38.8 +/- 19.0 versus 26.8 +/- 15.0 mEq/24 h) and ammonium (41.6 +/- 17.6 versus 34.2 +/-12.4 mmol/24 h). Logistic regression analysis with the presence of hypertension as the dependent variable produced a model with the following predictors: age (P < 0.0001), BMI (P = 0.026), titratable acid (P = 0.025) and low urinary citrate level (P = 0.033). Urinary acid excretion increased with the stage of hypertension. No difference was found in the urinary excretion of other solutes. CONCLUSIONS: These findings suggest that essential hypertension and acid excretion are linked in stone formers.