ABSTRACT
Chronic lithium treatment for bipolar disease causes mainly side effects in the kidney. A subset of lithium users develops nephrogenic diabetes insipidus (NDI), a urinary concentrating disorder, and chronic kidney disease (CKD). Age, lithium dose, and duration of treatment are important risk factors, whereas genetic background might also play an important role. To investigate the role of genetics, female mice of 29 different inbred strains were treated for 1 year with control or lithium chow and urine, blood, and kidneys were analyzed. Chronic lithium treatment increased urine production and/or reduced urine osmolality in 21 strains. Renal histology showed that lithium increased interstitial fibrosis and/or tubular atrophy in eight strains, whereas in none of the strains glomerular injury was induced. Interestingly, lithium did not elevate urinary albumin-creatinine ratio (ACR) in any strain, whereas eight strains even demonstrated a lowered ACR. The protective effect on ACR coincided with a similar decrease in urinary IgG levels, a marker of glomerular function, whereas the adverse effect of lithium on interstitial fibrosis/tubular atrophy coincided with a severe increase in urinary ß2-microglobulin (ß2M) levels, an indicator of proximal tubule damage. Genetic background plays an important role in the development of lithium-induced NDI and chronic renal pathology in female mice. The strong correlation of renal pathology with urinary ß2M levels indicates that ß2M is a promising biomarker for chronic renal damage induced by lithium.
Subject(s)
Diabetes Insipidus, Nephrogenic/chemically induced , Diabetes Insipidus, Nephrogenic/genetics , Genetic Background , Lithium/adverse effects , Renal Insufficiency, Chronic/chemically induced , Renal Insufficiency, Chronic/genetics , Animals , Biomarkers/urine , Bipolar Disorder/drug therapy , Diabetes Insipidus, Nephrogenic/blood , Diabetes Insipidus, Nephrogenic/urine , Disease Models, Animal , Female , Immunoglobulin G/urine , Lithium/blood , Lithium/therapeutic use , Mice , Mice, Inbred Strains , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/urine , beta 2-Microglobulin/urineABSTRACT
OBJECTIVES: We report a case of an infant with nephrogenic diabetes insipidus (NDI) diagnosed by the measurement of serum copeptin. There is only one study that previously evaluated the use of copeptin measurement in a pediatric patient. CASE PRESENTATION: We present a 10-month-old child with polyuria-polydipsia syndrome (PPS) and hypernatremia that could not support water restriction due to increased risk of dehydration and worsening of his condition. Therefore, plasma measurement of copeptin allowed the diagnosis of NDI. CONCLUSIONS: The water deprivation test (WDT) is considered the gold standard for diagnosis in PPS. However, WDT has serious limitations regarding its interpretation. Furthermore, the WDT can cause dehydration and hypernatremia, especially in young children. Therefore, the measurement of plasma copeptin seems to be a promising method to perform an earlier, safer, and accurate investigation of PPS. Up to now, our study is the second to report the usefulness of copeptin in children.
Subject(s)
Diabetes Insipidus, Nephrogenic/diagnosis , Glycopeptides/blood , Biomarkers/blood , Diabetes Insipidus, Nephrogenic/blood , Diagnostic Tests, Routine , Humans , Infant , Male , Polydipsia/blood , Polydipsia/diagnosis , Polyuria/blood , Polyuria/diagnosisABSTRACT
The two main differential diagnoses of central diabetes insipidus are nephrogenic diabetes insipidus and primary polydipsia. Reliable distinction between those entities is essential as treatment differs substantially with the wrong treatment potentially leading to serious complications. Past diagnostic measures using the indirect water deprivation test had several pitfalls, resulting in a low diagnostic accuracy. With the introduction of copeptin, a stable and reliable surrogate marker for arginine vasopressin, diagnosis of diabetes insipidus was new evaluated. While unstimulated basal copeptin measurement reliably diagnoses nephrogenic diabetes insipidus, a stimulation test is needed to differentiate patients with central diabetes insipidus from patients with primary polydipsia. Stimulation can either be achieved through hypertonic saline infusion or arginine infusion. While the former showed high diagnostic accuracy and superiority over the indirect water deprivation test in a recent validation study, the diagnostic accuracy for arginine-stimulated copeptin was slightly lower, but superior in test tolerance. In summary of the recent findings, a new copeptin based diagnostic algorithm is proposed for the reliable diagnosis of diabetes insipidus.
Subject(s)
Diabetes Insipidus/diagnosis , Diagnostic Techniques, Endocrine , Biomarkers/analysis , Biomarkers/blood , Diabetes Insipidus/blood , Diabetes Insipidus/etiology , Diabetes Insipidus, Nephrogenic/blood , Diabetes Insipidus, Nephrogenic/diagnosis , Diabetes Insipidus, Nephrogenic/etiology , Diabetes Insipidus, Neurogenic/blood , Diabetes Insipidus, Neurogenic/diagnosis , Diabetes Insipidus, Neurogenic/etiology , Diagnosis, Differential , Diagnostic Techniques, Endocrine/trends , Humans , Neurophysins/blood , Neurophysins/physiology , Polyuria/blood , Polyuria/diagnosis , Polyuria/etiology , Protein Precursors/blood , Protein Precursors/physiology , Vasopressins/blood , Vasopressins/physiologyABSTRACT
BACKGROUND: Differential diagnosis of diabetes insipidus is challenging. The most reliable approach is hypertonic saline-stimulated copeptin measurements. However, this test is based on the induction of hypernatraemia and requires close monitoring of plasma sodium concentrations. Arginine-stimulated copeptin measurements might provide an alternative, simple, and safe test. METHODS: In this prospective diagnostic study, we recruited a development cohort from University Hospital Basel, Basel, Switzerland, and a validation cohort from five centres in Basel, Aarau, Luzern, Bern, and St Gallen, Switzerland, and the University Hospital Würzburg, Würzburg, Germany. For both cohorts, patients were eligible for inclusion if they were aged 18 years or older, were newly referred with polyuria (>50 mL/kg bodyweight per day) or had a known diagnosis of central diabetes insipidus or primary polydipsia. We also recruited a comparator cohort of healthy controls in parallel to each cohort, comprising adults (aged 18 years and older, with normal drinking habits, and no history of polyuria) and children who underwent arginine stimulation to diagnose growth hormone deficiency (children were only included in the comparator cohort to the development cohort as proof of concept). Patients and healthy controls underwent arginine stimulation with measurement of plasma copeptin at baseline and 30, 45, 60, 90, and 120 min. The primary objective in the development cohort was to determine the diagnostic accuracy of plasma copeptin concentrations to discriminate between diabetes insipidus and primary polydipsia, and in the validation cohort was to confirm those results. Adverse effects of the test were monitored in all participants, with tolerability of the test rated using a visual analogue scale (VAS) that ranged from no (0) to maximum (10) discomfort. This trial is registered with ClinicalTrials.gov, number NCT00757276. FINDINGS: Between May 24, 2013, and Jan 11, 2017, 52 patients were enrolled in the development cohort (12 [23%] with complete diabetes insipidus, nine [17%] with partial diabetes insipidus, and 31 [60%] with primary polydipsia) alongside 20 healthy adults and 42 child controls. Between Oct 24, 2017, and June 27, 2018, 46 patients were enrolled in the validation cohort (12 [26%] with complete diabetes insipidus, seven [15%] with partial diabetes insipidus, and 27 [59%] with primary polydipsia) alongside 30 healthy adult controls (two patients in this cohort were excluded from the main analysis because of early vomiting during the test). In the pooled patient and control datasets, median arginine-stimulated copeptin concentrations increased in healthy adult controls (from 5·2 pM [IQR 3·3-10·9] to a maximum of 9·8 pM [6·4-19·6]) and in participants with primary polydipsia (from 3·6 pM [IQR 2·4-5·7] to a maximum of 7·9 pM [5·1-11·8]), but only minimally in those with diabetes insipidus (2·1 pM [IQR 1·9-2·7] to a maximum of 2·5 pM [1·9-3·1]). In the development cohort, a cutoff of 3·5 pM at 60 min provided the highest diagnostic accuracy of 94% (95% CI 84-98). The accuracy of this cutoff in the validation cohort was 86% (95% CI 73-94). By pooling the data from both cohorts, an optimal accuracy of 93% (95% CI 86-97) was reached at a cutoff of 3·8 pM copeptin at 60 min (sensitivity 93%, 95% CI 86-98; specificity 92%, 95% CI 84-100). The test was safe and well tolerated, with median VAS scores of 3·5 (IQR 2-4) in patients with diabetes insipidus, 3 (2-4) in those with primary polydipsia, 1 (1-3) in healthy adults, and 1 (0-5) in healthy children in the pooled participant dataset. INTERPRETATION: Arginine-stimulated copeptin measurements are an innovative test for diabetes insipidus with high diagnostic accuracy, and could be a simplified, novel, and safe diagnostic approach to diabetes insipidus in clinical practice. FUNDING: Swiss National Science Foundation and University Hospital Basel.
Subject(s)
Arginine/administration & dosage , Diabetes Insipidus, Nephrogenic/diagnosis , Glycopeptides/blood , Adult , Aged , Case-Control Studies , Diabetes Insipidus, Nephrogenic/blood , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Prospective Studies , Sensitivity and Specificity , Young AdultABSTRACT
OBJECTIVE: The water deprivation test (WDT) is widely used for the differential diagnosis of the polyuria-polydipsia syndrome (PPS). However, it is inconvenient and may not always be precise in differentiating partial forms of diabetes insipidus (DI) from primary polydipsia (PP). The aim of this study was to evaluate the results of a combined outpatient and inpatient overnight WDT protocol that included an overnight unsupervised period concerning its feasibility and safety. METHODS: We performed a retrospective analysis of clinical data and laboratory results of 52 patients with PPS undergoing WDT at a single center. RESULTS: PP was the most frequent diagnosis, followed by complete central DI (cCDI), partial central DI (pCDI), and nephrogenic DI (NDI). Over 90% of the patients showed an expected increase in serum osmolality at the end of the dehydration period. There were no reports of complications during the overnight deprivation period. Post-dehydration urine osmolality and urine-to-serum osmolality ratio significantly differentiated all the groups ( P<.05), except for cCDI and NDI, which could be differentiated by basal and post-dehydration vasopressin (AVP) levels ( P<.05 for both). Although these measurements were useful for differentiating patients according to their allocation groups, results from WDT and direct AVP levels may often require a comprehensive diagnostic approach, particularly in the challenging groups of PP and pCDI. CONCLUSION: A combined outpatient and inpatient overnight WDT protocol is safe and feasible when the test is performed with special care at experienced centers. Newer diagnostic tools are expected to improve the accuracy of PPS diagnosis. ABBREVIATIONS: AQP2 = aquaporin-2; AVP = vasopressin; CDI = central diabetes insipidus; cCDI = complete central diabetes insipidus; DDAVP = desmopressin; DI = diabetes insipidus; IQR = interquartile range; MRI = magnetic resonance imaging; Na+ = sodium; NDI = nephrogenic diabetes insipidus; pCDI = partial central diabetes insipidus; PP = primary polydipsia; PPS = polyuria-polydipsia syndrome; S_osm = serum osmolality; U_osm = urine osmolality; WDT = water deprivation test.
Subject(s)
Ambulatory Care , Diabetes Insipidus, Nephrogenic/diagnosis , Diabetes Insipidus, Neurogenic/diagnosis , Hospitalization , Polydipsia, Psychogenic/diagnosis , Polyuria/diagnosis , Water Deprivation , Adolescent , Adult , Aged , Child , Diabetes Insipidus, Nephrogenic/blood , Diabetes Insipidus, Neurogenic/blood , Female , Humans , Male , Middle Aged , Neurophysins/blood , Osmolar Concentration , Polydipsia/blood , Polydipsia/diagnosis , Polydipsia, Psychogenic/blood , Polyuria/blood , Protein Precursors/blood , Retrospective Studies , Syndrome , Vasopressins/blood , Young AdultABSTRACT
CONTEXT: The polyuria-polydipsia syndrome comprises primary polydipsia (PP) and central and nephrogenic diabetes insipidus (DI). Correctly discriminating these entities is mandatory, given that inadequate treatment causes serious complications. The diagnostic "gold standard" is the water deprivation test with assessment of arginine vasopressin (AVP) activity. However, test interpretation and AVP measurement are challenging. OBJECTIVE: The objective was to evaluate the accuracy of copeptin, a stable peptide stoichiometrically cosecreted with AVP, in the differential diagnosis of polyuria-polydipsia syndrome. DESIGN, SETTING, AND PATIENTS: This was a prospective multicenter observational cohort study from four Swiss or German tertiary referral centers of adults >18 years old with the history of polyuria and polydipsia. MEASUREMENTS: A standardized combined water deprivation/3% saline infusion test was performed and terminated when serum sodium exceeded 147 mmol/L. Circulating copeptin and AVP levels were measured regularly throughout the test. Final diagnosis was based on the water deprivation/saline infusion test results, clinical information, and the treatment response. RESULTS: Fifty-five patients were enrolled (11 with complete central DI, 16 with partial central DI, 18 with PP, and 10 with nephrogenic DI). Without prior thirsting, a single baseline copeptin level >21.4 pmol/L differentiated nephrogenic DI from other etiologies with a 100% sensitivity and specificity, rendering a water deprivation testing unnecessary in such cases. A stimulated copeptin >4.9 pmol/L (at sodium levels >147 mmol/L) differentiated between patients with PP and patients with partial central DI with a 94.0% specificity and a 94.4% sensitivity. A stimulated AVP >1.8 pg/mL differentiated between the same categories with a 93.0% specificity and a 83.0% sensitivity. LIMITATION: This study was limited by incorporation bias from including AVP levels as a diagnostic criterion. CONCLUSION: Copeptin is a promising new tool in the differential diagnosis of the polyuria-polydipsia syndrome, and a valid surrogate marker for AVP. Primary Funding Sources: Swiss National Science Foundation, University of Basel.
Subject(s)
Diabetes Insipidus, Nephrogenic/diagnosis , Diabetes Insipidus, Neurogenic/diagnosis , Glycopeptides/blood , Polydipsia/diagnosis , Polyuria/diagnosis , Adult , Arginine Vasopressin/blood , Cohort Studies , Diabetes Insipidus, Nephrogenic/blood , Diabetes Insipidus, Nephrogenic/complications , Diabetes Insipidus, Neurogenic/blood , Diabetes Insipidus, Neurogenic/complications , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Polydipsia/blood , Polydipsia/complications , Polyuria/blood , Polyuria/complications , Sensitivity and Specificity , Syndrome , Water Deprivation/physiologyABSTRACT
Previous studies of central diabetes insipidus suggested that thiazides acutely exerted a paradoxical antidiuresis by either indirectly activating volume-homeostatic reflexes to decrease distal fluid-delivery, or directly stimulating distal water-reabsorption. This study investigated whether the direct and indirect actions of bendroflumethiazide (BFTZ) simultaneously cooperated and also whether the renal nerves were involved in inducing long-term antidiuresis in nephrogenic diabetes insipidus (NDI). BFTZ or vehicle was gavaged into bilateral renal denervated and innervated rats with lithium-induced NDI for 10 days, constituting four groups. At one day before (D0) and one, five and ten days after starting administration of BFTZ or vehicle, rats were placed in metabolic cages to collect urine for 6 hours. BFTZ-treatment in both renal innervated and denervated rats caused equivalent reductions in urine-flow, creatinine clearance, lithium clearance and free-water clearance, but rises in urine-osmolality, fractional proximal reabsorption and fractional distal reabsorption at all days compared to D0, as well as to those of their relevant vehicle-received group. Therefore, the chronic antidiuretic response to BFTZ in conscious NDI rats was exerted through a concomitant cooperation of its direct distal effect of stimulating water-reabsorption and its indirect effect of reducing distal fluid-delivery by activating volume-homeostatic mechanisms, which appeared independent of the renal nerves.
Subject(s)
Antidiuretic Agents/pharmacology , Bendroflumethiazide/pharmacology , Diabetes Insipidus, Nephrogenic/drug therapy , Diuresis/drug effects , Kidney/drug effects , Lithium Chloride , Animals , Autonomic Denervation , Biomarkers/blood , Biomarkers/urine , Blood Pressure/drug effects , Blood Urea Nitrogen , Body Weight/drug effects , Creatinine/blood , Diabetes Insipidus, Nephrogenic/blood , Diabetes Insipidus, Nephrogenic/chemically induced , Diabetes Insipidus, Nephrogenic/physiopathology , Diabetes Insipidus, Nephrogenic/urine , Disease Models, Animal , Drinking/drug effects , Kidney/innervation , Kidney/metabolism , Kidney/physiopathology , Male , Natriuresis/drug effects , Osmolar Concentration , Rats , Rats, Sprague-Dawley , Time Factors , Urodynamics/drug effects , Water-Electrolyte Balance/drug effectsABSTRACT
Congenital nephrogenic diabetes insipidus is a rare, hereditary in nature, characterized by an inability of the kidney to concentrate urine, secondary to the manifold resistance to the action of vasopressin. X-linked forms of transmission (90%) are expressed in boys, from the neonatal period in general, by polyuria and polydipsia. Symptomatology in transmissive girls is variable but can sometimes be quite marked. These forms are secondary to mutations in the gene encoding the vasopressin V2 receptor, located at position Xq28, responsible for a loss of function of this receptor. Some of these mutations may cause a partial phenotype, less severe. Forms of autosomal, recessive or dominant are more rare (10%). Treatment is symptomatic, sometimes difficult in infants. It aims to avoid episodes of dehydration. It is based on a conventional diet hypo-osmotic and administration of hydrochlorothiazide and indomethacin. We report here the case of a child with congenital nephrogenic diabetes insipidus hospitalized at Children's Hospital of Rabat and throughout this case we review the pathophysiology and clinical and biological characteristics of the disease and including importance of contribution of clinical biochemistry laboratory in the diagnosis and monitoring of this disease.
Subject(s)
Diabetes Insipidus, Nephrogenic/diagnosis , Child , Clinical Laboratory Techniques/methods , Diabetes Insipidus, Nephrogenic/blood , Diabetes Insipidus, Nephrogenic/complications , Diabetes Insipidus, Nephrogenic/urine , Humans , Male , Monitoring, Physiologic/methods , Polydipsia/diagnosis , Polydipsia/etiology , Polyuria/diagnosis , Polyuria/etiologyABSTRACT
CONTEXT: Nephrogenic diabetes insipidus (NDI) is caused by partial or complete renal resistance to the effects of antidiuretic hormone. Acquired NDI can be caused by electrolyte imbalances (eg, hypercalcemia), renal/extrarenal diseases (eg, chronic pyelonephritis), and drugs (eg, lithium toxicity). Syphilis has never been reported to cause NDI. OBJECTIVE: The aim of this study was to report the case of a 56-year-old man with NDI secondary to syphilis. CASE: The 56-year-old patient presented with polyuria and polydipsia lasting more than 40 days. His urine specific gravity was 1.002. He had no history of chronic kidney disease or contact with toxicants. He had normal blood glucose levels. A water-deprivation test and vasopressin administration indicated NDI. His rapid plasma reagin titer was 1:128. The serum Treponema pallidum-particle agglutination test was positive. He reported engaging in unprotected, extramarital sex 6 months before polydipsia onset and thereafter developing a skin lesion on the external genitalia and arthralgia, both of which resolved spontaneously. Examination of renal biopsy specimens showed abundant plasmacytic and lymphocytic infiltration of the interstitium and low and flat tubular epithelial cells, indicating renal tubular injury. Silver staining revealed T. pallidum-like organisms. Immunohistochemical analysis with T. pallidum-specific antibody confirmed the presence of treponemes. INTERVENTION: The patient received 2.4 million U of benzathine penicillin im once a week for 3 weeks. RESULTS: His urine output gradually reduced; he recovered 1 month later. His urine specific gravity was 1.026, and his syphilis rapid plasma reagin titer was 1:8. CONCLUSION: Syphilis can cause NDI. The manifestations of syphilis and causes of acquired NDI are diverse.
Subject(s)
Diabetes Insipidus, Nephrogenic/microbiology , Kidney/microbiology , Syphilis/microbiology , Agglutination Tests , Anti-Bacterial Agents/therapeutic use , Antibodies, Bacterial/analysis , Biopsy , Diabetes Insipidus, Nephrogenic/blood , Diabetes Insipidus, Nephrogenic/pathology , Diabetes Insipidus, Nephrogenic/prevention & control , Humans , Kidney/pathology , Kidney/physiopathology , Male , Middle Aged , Penicillin G Benzathine/therapeutic use , Reagins/blood , Syphilis/drug therapy , Syphilis/immunology , Treatment Outcome , Treponema pallidum/immunology , Treponema pallidum/isolation & purificationABSTRACT
The exact mechanism underlying thiazides-induced paradoxical antidiuresis in diabetes insipidus is still elusive, but it has been hypothesized that it is exerted either via Na+-depletion activating volume-homeostatic reflexes to decrease distal delivery, or direct stimulation of distal water reabsorption. This study examined how these two proposed mechanisms actually cooperate to induce an acute bendroflumethiazide (BFTZ)-antidiuretic effect in nephrogenic diabetes insipidus (NDI). Anaesthetized rats with lithium (Li)-induced NDI were prepared in order to measure their renal functional parameters, and in some of them, bilateral renal denervation (DNX) was induced. After a 30 min control clearance period, we infused either BFTZ into 2 groups, NDI+BFTZ and NDI/DNX+BFTZ, or its vehicle into a NDI+V group, and six 30 min experimental clearance periods were taken. During BFTZ infusion in the NDI+BFTZ group, transiently elevated Na+ excretion was associated with rapidly increased urinary osmolality and decreased free water clearance, but Li clearance and urine flow declined in the later periods. However, in the NDI/DNX+BFTZ group, there was persistently elevated Na+ excretion with unchanged Li clearance and urine flow during the experimental period, while alterations in free water clearance and urinary osmolality resembled those in the NDI+BFTZ group. In conclusion, BFTZ initially exerted two direct effects of natriuresis-diuresis and stimulating free water reabsorption at the distal nephron in NDI, which together elevated Na+ excretion and urinary osmolality but kept the urine volume unchanged in the first hour. Thereafter, the resultant sodium depletion led to the activation of neural reflexes that reduced distal fluid delivery to compensate for BFTZ-induced natriuresis-diuresis which, in cooperation with the direct distal BFTZ-antidiuretic effect, resulted in excretion of urine with a low volume, high osmolality, and normal sodium.
Subject(s)
Bendroflumethiazide/pharmacology , Diabetes Insipidus, Nephrogenic/urine , Diuretics/pharmacology , Lithium Chloride/administration & dosage , Animals , Diabetes Insipidus, Nephrogenic/blood , Diabetes Insipidus, Nephrogenic/chemically induced , Diuresis/drug effects , Kidney/drug effects , Kidney/innervation , Kidney/metabolism , Lithium Chloride/blood , Natriuresis/drug effects , Osmolar Concentration , Rats , Rats, Sprague-Dawley , Sodium/blood , Sodium/metabolism , Sodium/urine , Water/metabolismABSTRACT
INTRODUCTION: After 40 years of use of lithium in the treatment of mood disorders, the renal risks associated with the long-term exposure to lithium are better known. OBJECTIVE: This review is aimed at summarizing the information available in the literature regarding the impact of lithium on renal structure and function, the prevalence of renal abnormalities, the associated risk-factors and the strategy for their identification and management. METHOD: Articles were selected using a Medline search. The keywords were lithium, renal function, kidney, nephrotoxicity, renal insufficiency, side-effects, polyuria, diabetes insipidus and drug monitoring. RESULT: A well-recognized adverse effect of lithium exposure is the occurrence of nephrotic diabetes insipidus (NDI) resulting in polyuria and polydipsia, which occurs in 20% of the patients on long-term lithium treatment. This side-effect is linked to a deficit in urine concentrating ability. Its occurrence is associated with the duration of lithium therapy. Although this effect of lithium is initially functional and may disappear if the treatment is rapidly stopped, it may become structural and permanent over time. The decision to stop lithium or to treat the NDI with amiloride is mainly based upon its functional impact. DISCUSSION: A debate has been ongoing for decades regarding whether or not the long-term use of lithium may cause slowly progressive renal failure. According to the recent literature, progressive renal failure occurs in approximately 20% of the patients on long-term lithium treatment, among whom a few develop severe renal insufficiency due to lithium (possibly in conjunction with other somatic factors) in the form of interstitial nephritis. However, there is an increasing number of reports of patients requiring dialysis after long-term exposure to lithium. CONCLUSION: Current recommended strategies for minimising the renal side effects of lithium include: avoiding acute episodes of renal toxicity; monitoring serum lithium concentrations in order to achieve optimal efficacy at the lowest possible concentrations; monitoring serum creatinine levels at least on a yearly basis, with discontinuation of lithium use, discussion with a nephrologist if creatinine clearance decreases below 60 ml/mn; and the possible application of lithium into single daily dose.
Subject(s)
Antimanic Agents/adverse effects , Bipolar Disorder/drug therapy , Kidney Failure, Chronic/chemically induced , Lithium Carbonate/adverse effects , Amiloride/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antimanic Agents/pharmacokinetics , Antimanic Agents/therapeutic use , Bipolar Disorder/blood , Diabetes Insipidus, Nephrogenic/blood , Diabetes Insipidus, Nephrogenic/chemically induced , Diabetes Insipidus, Nephrogenic/drug therapy , Diuretics/therapeutic use , Dose-Response Relationship, Drug , Drug Therapy, Combination , Humans , Indomethacin/therapeutic use , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/drug therapy , Kidney Function Tests , Lithium Carbonate/pharmacokinetics , Lithium Carbonate/therapeutic use , Long-Term Care , Nephrotic Syndrome/blood , Nephrotic Syndrome/chemically induced , Nephrotic Syndrome/drug therapy , Potassium/therapeutic use , Risk FactorsABSTRACT
Hyperuricemia (HU) is considered to be a sign of metabolic syndrome as a consequence of purine metabolism disorder. To investigate alterations in uric acid (UA) methabolism, 90 subjects (M/F 53/37, aged 58 +/- 4 yr) with type 2 diabetes mellitus (DM2) were divided into 5 groups depending on the amount of excreted UA and its content in blood plasma. HU was found in 29% of patients, while hyperpoduction of UA was characteristic in 87% patients. Normo- or hypouricemia in majority of patients were mostly connected to kidney hyperfiltration and "compensatory" hyperuricosuria. HU with decreased UA excretion ("kidney" HU) was characteristic of severe DM2 with reduced kidney filtration rate. "Metabolic" HU with increased formation and excretion rated of UA was observed only in obese men. Increased insulinemia levels and insulin resistance index (IR) were found in obese patients in comparison with subjects with normal weight, independently of the type of UA excretion disorder. IR strongly correlated with serum UA levels in all groups of patients. The results suggest the significance of insulin resistance and abdominal obesity in UA metabolism in DM2.
Subject(s)
Diabetes Insipidus, Nephrogenic/metabolism , Hyperuricemia/metabolism , Metabolic Syndrome/metabolism , Uric Acid/blood , Abdominal Fat/metabolism , Aged , Diabetes Insipidus, Nephrogenic/blood , Female , Humans , Hyperuricemia/blood , Insulin Resistance , Male , Metabolic Syndrome/blood , Middle Aged , Obesity/blood , Obesity/metabolism , Uric Acid/metabolismABSTRACT
We report a case of a 75-year-old male patient who presented to the emergency room with arterial hypotension and impaired vigilance. The patient was on lithium therapy due to mood disorder. One month earlier medication with a betablocker, a loop-diuretic and an ACE-inhibitor had been started due to heart failure. Findings at admission included renal insufficiency, pneumonia and a slightly increased serum level of lithium. Three days later his Glasgow Coma Scale Score was 7, he showed gaze deviation, increased muscle tonus and cloni. The patient fully recovered after volume substitution and normalization of his renal function. Diagnosis of chronic intoxication with lithium was made due to the clinical picture and after exclusion of neurological pathologies. The pharmacokinetic characteristics of lithium is described and the risk factors leading to lithium intoxication and treatment of intoxication are discussed.
Subject(s)
Antimanic Agents/toxicity , Bipolar Disorder/drug therapy , Consciousness Disorders/chemically induced , Diabetes Insipidus, Nephrogenic/chemically induced , Emergencies , Hypotension/chemically induced , Lithium Carbonate/toxicity , Tachycardia/chemically induced , Acute Kidney Injury/blood , Acute Kidney Injury/chemically induced , Acute Kidney Injury/diagnosis , Aged , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/adverse effects , Antimanic Agents/administration & dosage , Antimanic Agents/pharmacokinetics , Bipolar Disorder/blood , Consciousness Disorders/blood , Consciousness Disorders/diagnosis , Creatinine/blood , Diabetes Insipidus, Nephrogenic/blood , Diabetes Insipidus, Nephrogenic/diagnosis , Diagnosis, Differential , Diuretics/administration & dosage , Diuretics/adverse effects , Drug Therapy, Combination , Humans , Hyperkalemia/blood , Hyperkalemia/chemically induced , Hypernatremia/blood , Hypernatremia/chemically induced , Hypernatremia/diagnosis , Hypotension/blood , Hypotension/diagnosis , Kidney Concentrating Ability/drug effects , Lithium Carbonate/administration & dosage , Lithium Carbonate/pharmacokinetics , Male , Myelinolysis, Central Pontine/blood , Myelinolysis, Central Pontine/chemically induced , Myelinolysis, Central Pontine/diagnosis , Sulfonamides/administration & dosage , Sulfonamides/adverse effects , Tachycardia/blood , Tachycardia/diagnosis , TorsemideABSTRACT
We performed mutational analyses of a woman patient with congenital nephrogenic diabetes insipidus referred to us during pregnancy. The diagnosis was made during the neonatal period, after which she was treated with spironolactone and hydrochlorothiazide. Our examination showed the patient to be apparently in good health without definite evidence of dehydration. Serum and urine osmolality were 220 mOsm/L and 50 mOsm/L, respectively, and the serum concentration of AVP was 2.7 pg/mL. Results of a water-deprivation test performed after delivery were compatible with nephrogenic diabetes insipidus. Mutational analyses showed that the patient was a compound heterozygote with point mutations at nucleotide position 298 (G to A; G100R) in exon 1 and nucleotide position 374 (C to T; T125M) in exon 2 of the aquaporin 2 gene, which have been previously described.
Subject(s)
Aquaporin 2/genetics , Diabetes Insipidus, Nephrogenic/genetics , Mutation , Adult , Aquaporin 2/blood , DNA Mutational Analysis , Diabetes Insipidus, Nephrogenic/blood , Diabetes Insipidus, Nephrogenic/congenital , Female , Genetic Predisposition to Disease , Heterozygote , Humans , Infant, Newborn , Male , Pregnancy , Pregnancy Complications , Pregnancy OutcomeABSTRACT
About 90% of patients with congenital nephrogenic diabetes insipidus (NDI) have vasopressin type 2 receptor (V2R) gene mutations that are inherited in an X-linked recessive manner. Although most female carriers are asymptomatic, some female carriers show polydipsia and polyuria. The reason why female carriers show NDI symptoms is explained by skewed X-inactivation. We studied X-inactivation patterns of six female carriers with heterozygote V2R gene mutations. The X-inactivation pattern in peripheral blood leukocytes was examined using methylation analysis of the polymorphic CAG repeat in the androgen receptor gene. Two asymptomatic female carriers showed random X-inactivation (61.9% and 60.7%). Skewed X-inactivation patterns (71.6%, 79.4%, and 91.2%) occurring preferentially to normal X alleles were recognized in three female carriers who showed clinical NDI symptoms. However, in one female carrier who showed clinical NDI symptoms, random X-inactivation (55.4%) was recognized. In conclusion, the clinical NDI phenotypes may correlate with the X-inactivation patterns in female carriers with heterozygote V2R gene mutations. However, in some female carriers, we cannot predict the clinical phenotypes by the evaluation of the X-inactivation patterns in peripheral blood leukocytes, because X-inactivation ratios within an individual are sometimes different between tissues.
Subject(s)
Diabetes Insipidus, Nephrogenic/genetics , Heterozygote , Mutation/genetics , Phenotype , Receptors, Vasopressin/genetics , X Chromosome Inactivation/genetics , Adult , Child , Diabetes Insipidus, Nephrogenic/blood , Female , Genes, X-Linked/genetics , Humans , Infant , Leukocytes, Mononuclear/metabolism , Male , Pedigree , Receptors, Vasopressin/metabolismABSTRACT
BACKGROUND: Sickle cell disease (SCD) affects the kidney by acute mechanisms as well as by insidious renal medullary/papillary necrosis, resulting in tubular defects, which increase the risk of dehydration and subsequent sickle crisis. Hypoxia has been reported to stimulate endothelin-1 (ET-1) synthesis by endothelial cells and also in the renal tubule. METHODS: This case-control study measured ET-1 in urine as a marker of its renal synthesis in asymptomatic SCD patients. Baseline plasma and urinary ET-1 levels were measured and followed during a water deprivation study and a subsequent administration of desmopressin. RESULTS: Urine and plasma levels of ET-1 were elevated in patients with SCD, compared with carefully matched African-French and African controls, and urine ET-1 excretion was associated with a marked urine-concentrating defect. Moreover, urinary ET-1 output was correlated with microalbuminuria in SCD patients. CONCLUSIONS: ET-1 is known to antagonize the tubular effects of vasopressin and to promote renal scarring; increased renal production of ET-1 could produce nephrogenic diabetes insipidus and dehydration in SCD patients through a combination of fibrosis and functional resistance to vasopressin. This study provides a rationale for trials with endothelin receptor antagonists in sickle cell disease nephropathy.
Subject(s)
Albuminuria/urine , Anemia, Sickle Cell/urine , Diabetes Insipidus, Nephrogenic/urine , Endothelin-1/urine , Adult , Albuminuria/blood , Albuminuria/etiology , Anemia, Sickle Cell/blood , Anemia, Sickle Cell/complications , Biomarkers/blood , Biomarkers/urine , Case-Control Studies , Diabetes Insipidus, Nephrogenic/blood , Diabetes Insipidus, Nephrogenic/complications , Disease Progression , Endothelin-1/biosynthesis , Endothelin-1/blood , Female , Humans , Kidney Tubules/metabolism , Male , Radioimmunoassay , Severity of Illness IndexSubject(s)
Amphotericin B/adverse effects , Antifungal Agents/adverse effects , Diabetes Insipidus, Nephrogenic/chemically induced , Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Diabetes Insipidus, Nephrogenic/blood , Humans , Kidney Tubules, Collecting/drug effects , Kidney Tubules, Collecting/metabolism , Mycoses/drug therapy , Potassium/metabolism , Sodium/metabolismABSTRACT
Although hemochromatosis is one of the most common genetic disorders in humans, the clinical information on iron-induced renal impairment is limited. We describe the clinical features of nephrogenic diabetes insipidus (NDI) observed in a case of hemochromatosis. A 57-year-old diabetic man was admitted to the hospital with a 6-month history of persistent polyuria, which had been sustained after glycemic optimization with insulin therapy and resulted in hepatic coma. Despite sufficient basal excretion of arginine vasopressin, impaired urinary concentrating capacity was observed, which could not be corrected by supraphysiologic doses of exogenous arginine vasopressin. Histochemical investigations showed widely distributed iron deposition in hepatocytes and moderately increased iron deposits in the tubular epithelium of distal urinary tubules and collecting ducts, suggesting that iron deposition resulting from hemochromatosis leads to NDI. This may be the first case report of NDI associated with hemochromatosis in humans. More attention should be paid to latent NDI as another complication of hemochromatosis.
Subject(s)
Diabetes Insipidus, Nephrogenic/etiology , Hemochromatosis/complications , Diabetes Insipidus, Nephrogenic/blood , Hemochromatosis/blood , Humans , Male , Middle AgedABSTRACT
A 47-year-old man presented with polydipsia, which had had since childhood, and recent onset of hypertension. Genetic analysis proved that he had nephrogenic diabetes insipidus caused by a novel mutation (deletion of 6 amino acids between G107 and C112) in the vasopressin V2 receptor gene. Results of 24-hour blood pressure monitoring disclosed a greater dipping pattern and greater blood pressure variability during waking hours than in male patients with only essential hypertension. This characteristic blood pressure profile may result from daily occurrence of free water depletion, as further observation indicated that water deprivation was associated with a reduction in blood pressure.