Prevalence of renal impairment is increasing with aging in sickle cell anemia (SCA) patients, and is responsible for a high morbidity and mortality. However, sickle cell nephropathy's natural course ...remains mostly unknown. We conducted a prospective observational cohort study aimed to identify risk factors for CKD stage II in a cohort of SCA patients. Baseline clinical and biological parameters were collected. Renal parameters were updated at each visit. Risk factors were analyzed using the Cox model. Five‐hundred and thirty‐five SCA patients were included with a median follow‐up of 5.33 (IQR:2.10–8.13) years. Median age was 22 (IQR:19–30) years old. Glomerular hyperfiltration was detected in 299 (55.9%) patients, microalbuminuria and macroalbuminuria in 180 (34%) and 67 (12.7%) patients respectively. During follow up, CKD stage II onset was detected in 39 patients (7.3%). Risk factors for CKD stage II after adjustment on baseline eGFR and age were macroalbuminuria HR: 3.89 95% CI: 1.61;9.43, diastolic blood pressure (DBP) above 70 mm Hg HR: 2.02 1.02–3.971, LDH (for 100 IU/L increase) HR: 1.28 1.12;1.48 and tricuspid regurgitation velocity >2.5 m/sec HR: 2.89 1.20–6.99. Multivariate analysis also found age as a strong independent risk factor with HR: (per year increase) 1.13 1.09;1.16 and a 13.3‐fold increase above 30 years (p < 0.001). Our results show a high incidence of CKD stage II with aging, with a strong significant risk increase after 30‐years‐old, and pinpoint baseline DBP, macroalbuminuria and increased LDH as independent risk factors raising the issue of optimal blood pressure targets for SCA patients.
Recent studies suggest that alkalinizing treatments improve the course of chronic kidney disease (CKD), even in patients without overt metabolic acidosis. Here, we tested whether a decreased ability ...in excreting urinary acid rather than overt metabolic acidosis may be deleterious to the course of CKD. We studied the associations between baseline venous total CO2 concentration or urinary ammonia excretion and long-term CKD outcomes in 1065 patients of the NephroTest cohort with CKD stages 1–4. All patients had measured glomerular filtration rate (mGFR) by 51Cr-EDTA renal clearance. Median mGFR at baseline was 37.6 ml/min per 1.73 m2. Urinary ammonia excretion decreased with GFR, whereas net endogenous acid production did not. After a median follow-up of 4.3 years, 201 patients reached end-stage renal disease (ESRD) and 114 died before ESRD. Twenty-six percent of the patients had mGFR decline rate greater than 10% per year. Compared with patients in the highest tertile of urinary ammonia excretion, those in the lowest tertile had a significantly increased hazard ratio for ESRD, 1.82 (95% CI, 1.06–3.13), and a higher odds ratio of fast mGFR decline, 1.84 (0.98–3.48), independent of mGFR and other confounders. Patients in the lowest tertile of venous total CO2 had significantly increased risk of fast mGFR decline but not of ESRD. None of these biomarkers was associated with mortality. Thus, these results suggest that the inability to excrete the daily acid load is deleterious to renal outcomes.
Abstract Background The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of hyponatremia in clinical practice, but current management of hyponatremia and ...outcomes in patients with SIADH are not well understood. The objective of the Hyponatremia Registry was to assess the current state of management of hyponatremia due to SIADH in diverse hospital settings, specifically: which diagnostic and treatment modalities are currently employed and how rapidly and reliably they result in an increase in serum Na+ . A secondary objective was to determine whether treatment choices and outcomes differ across the United States (US) and the European Union (EU). Methods The HN Registry recorded selected diagnostic measures and utilization, efficacy, and outcomes of therapy for euvolemic HN diagnosed clinically as SIADH in 1,524 adult patients with serum sodium concentration (Na+ ) ≤130 mEq/L (1,034 from 146 US and 490 from 79 EU sites). A subgroup of patients with more rigorously defined SIADH via measurement of relevant laboratory parameters was also analyzed. Results The most common monotherapy treatments for hyponatremia in SIADH were fluid restriction (48%), isotonic (27%) or hypertonic (6%) saline, and tolvaptan (13%); 11% received no active agent. The mean rate of Na+ change (mEq/L/d) was greater for all active therapies than no active treatment. Hypertonic saline and tolvaptan produced the greatest mean rate of Na+ change (IQR both 3.0(6.0) mEq/L/d), compared to lower IQR rates of Na+ change for isotonic saline (1.5(3.0) mEq/L/d) and fluid restriction (1.0(2.3) mEq/L/d). The general pattern of responses was similar in both the US and EU cohorts. At discharge, Na+ was <135 mEq/L in 75% of patients and ≤130 mEq/L in 43%. Overly rapid correction occurred in 10.2%. Conclusions 1) Current treatment of hyponatremia in SIADH often employs therapies with limited efficacy; the most commonly chosen monotherapy treatments, fluid restriction and isotonic saline, failed to increase the serum Na+ by ≥5 mEq/L in 55% and 64% of monotherapy treatment episodes, respectively. 2) Appropriate laboratory tests to diagnose SIADH were obtained in <50% of patients; success rates in correcting hyponatremia were significantly higher when such tests were obtained. 3) Few outcome differences were found between the US and EU. A notable exception was hospital length of stay; use of tolvaptan was associated with significantly shorter length of stay in the EU but not the US. 4) Despite the availability of effective therapies, most patients with SIADH were discharged from the hospital still hyponatremic.
Objective
Familial hypocalciuric hypercalcaemia type 1 (FHH1), related to heterozygous loss‐of‐function mutations of the calcium‐sensing receptor gene, is the main differential diagnosis for primary ...hyperparathyroidism. The aim of our study was to describe clinical characteristics of adult patients living in France with a genetically confirmed FHH1.
Design and patients
This observational, retrospective, multicentre study included 77 adults, followed up in 32 clinical departments in France, with a genetic FHH1 diagnosis between 2001 and 2012.
Results
Hypercalcaemia was diagnosed at a median age of 53 years IQR: 38‐61. The diagnosis was made after clinical manifestations, routine analysis or familial screening in 56, 34 and 10% of cases, respectively, (n = 58; data not available for 19 patients). Chondrocalcinosis was present in 11/51 patients (22%), bone fractures in 8/56 (14%) and renal colic in 6/55 (11%). The median serum calcium was 2.74 mmol/L IQR: 2.63‐2.86 mmol/L, the median plasma parathyroid hormone level was 4.9 pmol/L 3.1‐7.1, and the median 24‐hour urinary calcium excretion was 2.8 mmol/24 hours IQR: 1.9‐4.0. Osteoporosis (dual X‐ray absorptiometry) or kidney stones (renal ultrasonography) were found in 6/38 patients (16%) and 9/32 patients (28%), respectively. Fourteen patients (18%) underwent parathyroid surgery; parathyroid adenoma was found in three patients (21%) and parathyroid hyperplasia in nine patients (64%). No correlation between genotype and phenotype was established.
Conclusion
This large cohort study demonstrates that FHH1 clinical characteristics can be atypical in 33 patients (43%). Clinicians should be aware of this rare differential diagnosis in order to adopt an appropriate treatment strategy.
Timing of Onset of CKD-Related Metabolic Complications MORANNE, Olivier; FROISSART, Marc; FOUQUERAY, Bruno ...
Journal of the American Society of Nephrology,
2009, 2009-Jan, 2009-01-00, 20090101, 2009-01, Volume:
20, Issue:
1
Journal Article
Peer reviewed
Open access
Chronic kidney disease (CKD) guidelines recommend evaluating patients with GFR <60 ml/min per 1.73 m(2) for complications, but little evidence supports the use of a single GFR threshold for all ...metabolic disorders. We used data from the NephroTest cohort, including 1038 adult patients who had stages 2 through 5 CKD and were not on dialysis, to study the occurrence of metabolic complications. GFR was measured using renal clearance of (51)Cr-EDTA (mGFR) and estimated using two equations derived from the Modification of Diet in Renal Disease study. As mGFR decreased from 60 to 90 to <20 ml/min per 1.73 m(2), the prevalence of hyperparathyroidism increased from 17 to 85%, anemia from 8 to 41%, hyperphosphatemia from 1 to 30%, metabolic acidosis from 2 to 39%, and hyperkalemia from 2 to 42%. Factors most strongly associated with metabolic complications, independent of mGFR, were younger age for acidosis and hyperphosphatemia, presence of diabetes for acidosis, diabetic kidney disease for anemia, and both male gender and the use of inhibitors of the renin-angiotensin system for hyperkalemia. mGFR thresholds for detecting complications with 90% sensitivity were 50, 44, 40, 39, and 37 ml/min per 1.73 m(2) for hyperparathyroidism, anemia, acidosis, hyperkalemia, and hyperphosphatemia, respectively. Analysis using estimated GFR produced similar results. In summary, this study describes the onset of CKD-related complications at different levels of GFR; anemia and hyperparathyroidism occur earlier than acidosis, hyperkalemia, and hyperphosphatemia.
Background
Lithium therapy during bipolar disorder is associated with an increased risk of chronic kidney disease (CKD) that is slowly progressive and undetectable at early stages. We aimed at ...identifying kidney image texture features as possible imaging biomarkers of decreased measured glomerular filtration rate (mGFR) using radiomics of T2‐weighted magnetic resonance imaging (MRI).
Methods
One hundred and eight patients treated with lithium were evaluated including mGFR and kidney MRI, with T2‐weighted sequence single‐shot fast spin‐echo. Computed radiomic analysis was performed after kidney segmentation. Significant features were selected to build a radiomic signature using multivariable Cox analysis to detect an mGFR <60 ml/min/1.73 m². The texture index was validated using a training and a validation cohort.
Results
Texture analysis index was able to detect an mGFR decrease, with an AUC of 0.85 in the training cohort and 0.71 in the validation cohort. Patients with a texture index below the median were older (59 42–66 vs. 46 34–54 years, p = .001), with longer treatment duration (10 3–22 vs. 6 2–10 years, p = .02) and a lower mGFR (66 46–84 vs. 83 71–94 ml/min/1.73m², p < .001). Texture analysis index was independently and negatively associated with age (β = −.004 ± 0.001, p < .001), serum vasopressin (−0.005 ± 0.002, p = .02) and lithium treatment duration (−0.01 ± 0.003, p = .001), with a significant interaction between lithium treatment duration and mGFR (p = .02).
Conclusions
A renal texture index was developed among patients treated with lithium associated with a decreased mGFR. This index might be relevant in the diagnosis of lithium‐induced renal toxicity.
Background
The underlying mechanisms of exercise intolerance in sickle cell anaemia (SCA) patients are complex and not yet completely understood. While latent heart failure at rest could be unmasked ...upon exercise, most previous studies assessed cardiac function at rest. We aimed to investigate exercise cardiovascular reserve as a potential contributor to exercise intolerance in adult SCA patients.
Methods
In this observational prospective study, we compared prospectively 60 SCA patients (median age 31 years, 60% women) to 20 matched controls. All subjects underwent symptom‐limited combined exercise echocardiography and oxygen uptake (VO2) measurements. Differences between arterial and venous oxygen content (C(a‐v)O2) were calculated. Cardiac reserve was defined as the absolute change in cardiac index (Ci) from baseline to peak exercise.
Results
Compared to controls, SCA patients demonstrated severe exercise intolerance (median peakVO2, 34.3 vs. 19.7 ml/min/kg, respectively, p < .0001). SCA patients displayed heterogeneously increased Ci from rest to peak exercise (median +5.8, range 2.6 to 10.6 L/min/m²) which correlated with peakVO2 (r = 0.71, p < .0001). In contrast, the C(a‐v)O2 exercise reserve was homogenously reduced and did not correlate with peakVO2 (r = 0.18, p = .16). While haemoglobin level and C(a‐v)O2 were similar in SCA subgroups, SCA patients in the lower VO2 tertile had chronotropic incompetence and left ventricular diastolic dysfunction (left atrial peak longitudinal strain was reduced, and both E/e’ ratio and left atrial volume index were increased) and were characterized by a reduced cardiac reserve, +5.04.2–5.5 compared to +6.75.5–7.8 L/min/m² for the rest of the patient cohort, p < .0001.
Conclusions
Altered cardiac reserve due to chronotropic incompetence and left ventricular diastolic dysfunction seems to be an important determinant of exercise intolerance in adult SCA patients.
Cotrimoxazole (Trimethoprim/Sulfamethoxazole-SMX) is frequently used in critically ill and immunocompromised patients. SMX is converted to N-acetyl-sulfamethoxazole (NASM) and excreted by the ...kidneys. NASM may form crystals in urine, especially in acid urine, that may induce a crystalline nephropathy. However, the imputability of crystals in acute kidney injury (AKI) has not been proven. We aimed to assess whether NASM crystals may promote AKI and to investigate risk factors associated with NASM crystalline nephropathy. Patients from Ile-de-France, France who developed AKI under SMX treatment introduced during hospitalization and had a crystalluria positive for NASM crystals were selected. Patients with excessive preanalytical delay for crystalluria or missing data regarding SMX treatment were excluded. We used the Naranjo score to assess the causal relationship between SMX and the development of AKI in patients with positive NASM crystalluria. Fourteen patients were included. SMX was the probable cause of AKI for 11 patients and a possible cause for 3 patients according to Naranjo score. Patients were exposed to high doses of SMX (but within recommended ranges), and most of them had a preexisting chronic kidney disease and were hypoalbuminemic. Urine pH was mildly acid (median 5.9). AKI occured more rapidly than expected after introduction of SMX (median 4 days) and recovered rapidly after drug discontinuation in most, but not all, cases. SMX is a probable cause of crystalline nephropathy. Monitoring of crystalluria in patients exposed to SMX may be of interest to prevent the development of crystalline nephropathy. Approval number of the study: BPD-2018-DIAG-008.
The generalized use of physical methods, X-ray diffraction and Fourier transform infrared spectroscopy (FTIR) decisively improved urinary stone analysis by allowing to accurately identify the ...chemical nature, crystalline phases and relative proportions of stone constituents. Such compositional analysis is sufficient to identify stone diseases involving a single specific component such as cystine, 2,8-dihydroxyadenine (DHA), struvite, uric acid, ammonium hydrogen urate or a drug. However, for common calcium nephrolithiasis, which represents by far the largest part of urinary stones throughout the world, the simple identification of calcium oxalate (CaOx) and/or calcium phosphate (CaP) as constituents provides incomplete etiologic information because a same elemental stone composition may result from different lithogenic processes.
A more comprehensive method combining careful morphologic examination of the surface and the section of stones with detailed FTIR analysis of the nature, location, crystalline phases and a respective proportion of stone constituents, therefore termed ‘morpho-constitutional’ analysis, as used in our laboratory for four decades provides more complete etiologic information. In common idiopathic CaOx nephrolithiasis, the predominance of the monohydrate form (COM) was shown to be associated with elevated urine Ox concentration, whereas the dihydrate form (COD) was associated with hypercalciuria, thus orienting dietary and/or pharmacological intervention. A major contribution of the method is to immediately orient the diagnosis of rare, but severe, diseases leading to a loss of renal function, when stone analysis reveals a peculiar morphology of common constituents. The most salient examples are the type Ic morphology of COM stones, pathognomonic of primary hyperoxaluria, type Ie morphology, which is highly suggestive of absorptive hyperoxaluria as seen in inflammatory bowel diseases and pathologies inducing steatorrhea, type IIId morphology of ammonium urate stones, which orientates towards chronic diarrhea with dietary imbalance and loss of electrolytes, and type IVa2 morphology of carbapatite, specific of distal renal tubular acidosis of congenital or acquired origin, and distinctive aspect of 2,8-DHA stones. In conclusion, the proposed morpho-constitutional method should be recommended for routine stone analysis, inasmuch as it is simple, rapid, reliable, clinically relevant and cost-effective.
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