scholarly journals A Rare Case of Nephrogenic Diabetes Insipidus From Tenofovir

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A566-A566
Author(s):  
Izzah Vasim ◽  
Peggy Nana Ama Amoakohene ◽  
Janice McMillan ◽  
Gregory Hong
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Case Reports ◽  
Urine Osmolality ◽  
Adverse Outcomes ◽  
Fluid Restriction ◽  
Tubular Dysfunction ◽  
Renal Tubular Dysfunction ◽  
Drug Induced ◽  
Tenofovir Alafenamide

Abstract Introduction: Diabetes insipidus (DI) is a clinical condition which manifests as excessive urine output, either because of impaired or inadequate antidiuretic hormone (ADH) secretion, or an inability of the kidneys to respond to ADH. Nephrogenic DI is more often drug induced. Recent clinical reports have shown that medications like tenofovir may result in nephrogenic DI as well. Tenofovir is a well-known nucleoside reverse transcriptase inhibitor analog of adenosine used in the management of both human immunodeficiency virus (HIV) and chronic hepatitis B. With its increased use, reports of adverse outcomes have been documented, mainly its effect on renal function including nephrogenic DI, renal failure and Fanconi syndrome. We present a case of nephrogenic DI whilst on Biktarvy (a combination of bictegravir, emtricitabine and tenofovir alafenamide). Case: A 59-year-old African American female with a history of HIV on Biktarvy, T2DM, HLD, HTN, MI, CAD, COPD presented to our hospital with weakness and falls for 1-2 months associated with polydipsia and polyuria. She had started Biktarvy for HIV about 2 months ago after which her symptoms got worse. Labs showed a serum Na of 151, potassium of 3.2 on admission with serum osmolality of 323 and urine osmolality of 134. During hospitalization, she was challenged with 100ug oral Desmopressin. Urine labs failed to correct after Desmopressin administration which was highly indicative of severe nephrogenic DI. The challenge was repeated with 200ug oral Desmopressin with similar results. Pituitary DI was considered given the patient’s falls; however urine osmolality did not improve following desmopressin challenge. Furthermore, her serum Co-peptin level was elevated at 36.1 that ruled out central DI. The patient’s hypokalemia was believed to be driving her nephrogenic DI which has been reported in various case reports with patients on Tenofovir, but has never been reported in patients taking Biktarvy (which includes Tenofovir Alafenamide). She was subsequently placed on fluid restriction during which time the patient’s serum Na and Cr increased while urine osmolality did not correct. HCTZ was ultimately started as a treatment for nephrogenic DI and patient was transitioned of biktarvy to lamivudine and dolutegravir. Her polyuria and polydipsia improved, however she developed hyponatremia likely because of HCTZ. Patient concentrating ability improved off biktarvy and HCTZ was discontinued on the day prior to discharge without issue. Her subsequent serum sodium and potassium levels were normal. Conclusions: Our case highlights a rare incidence of tenofovir induced hypokalemia leading to nephrogenic DI. This case illustrates the importance of monitoring patients on tenofovir for signs of renal [tubular] dysfunction. In a polyuric patient on tenofovir, there should be a high index of suspicion for nephrogenic diabetes insipidus.

Serial Quantification of Urinary Protein Biomarkers to Predict Drug-induced Acute Kidney Injury

2019 ◽  
Vol 20 (8) ◽  
pp. 656-664 ◽  
Author(s):  
Yi Da ◽  
K. Akalya ◽  
Tanusya Murali ◽  
Anantharaman Vathsala ◽  
Chuen-Seng Tan ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Cystatin C ◽  
Calcineurin Inhibitors ◽  
Kidney Injury ◽  
Tubular Dysfunction ◽  
Renal Tubular Dysfunction ◽  
Protein Biomarkers ◽  
Drug Induced ◽  
Beta 2 ◽  
Beta 2 Microglobulin

Background: : Drug-induced Acute Kidney Injury (AKI) develops in 10-15% of patients who receive nephrotoxic medications. Urinary biomarkers of renal tubular dysfunction may detect nephrotoxicity early and predict AKI. Methods:: We prospectively studied patients who received aminoglycosides, vancomycin, amphotericin, or calcineurin inhibitors, and collected their serial urine while on therapy. Patients who developed drug-induced AKI (fulfilling KDIGO criteria) were matched with non-AKI controls in a 1:2 ratio. Their urine samples were batch-analyzed at time-intervals leading up to AKI onset; the latter benchmarked against the final day of nephrotoxic therapy in non- AKI controls. Biomarkers examined include clusterin, beta-2-microglobulin, KIM1, MCP1, cystatin-C, trefoil-factor- 3, NGAL, interleukin-18, GST-Pi, calbindin, and osteopontin; biomarkers were normalized with corresponding urine creatinine. Results:: Nine of 84 (11%) patients developed drug-induced AKI. Biomarkers from 7 AKI cases with pre-AKI samples were compared with those from 14 non-AKI controls. Corresponding mean ages were 55(±17) and 52(±16) years; baseline eGFR were 99(±21) and 101(±24) mL/min/1.73m2 (all p=NS). Most biomarker levels peaked before the onset of AKI. Median levels of 5 biomarkers were significantly higher in AKI cases than controls at 1-3 days before AKI onset (all µg/mmol): clusterin [58(8-411) versus 7(3-17)], beta-2-microglobulin [1632(913-3823) versus 253(61-791)], KIM1 [0.16(0.13-0.76) versus 0.07(0.05-0.15)], MCP1 [0.40(0.16-1.90) versus 0.07(0.04-0.17)], and cystatin-C [33(27-2990) versus 11(7-19)], all p<0.05; their AUROC for AKI prediction were >0.80 (confidence intervals >0.50), with average accuracy highest for clusterin (86%), followed by beta-2-microglobulin, cystatin-C, MCP1, and KIM1 (57%) after cross-validation. Conclusion: : Serial surveillance of these biomarkers could improve the lead time for nephrotoxicity detection by days.

scholarly journals MON-LB65 Lithium: The Culprit of Multiple Endocrinopathies

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Alice Yau ◽  
Gul Bahtiyar ◽  
Giovanna Rodriguez ◽  
Jose R Martinez Escudero
Keyword(s):  
Bipolar Disorder ◽  
Diabetes Insipidus ◽  
Mental Status ◽  
Nephrogenic Diabetes Insipidus ◽  
Kidney Injury ◽  
Urine Osmolality ◽  
Altered Mental Status ◽  
Clinical Findings ◽  
Volume Depletion ◽  
Collecting Tubules

Abstract Background: Lithium, commonly used to treat various psychiatric disorders such as bipolar disorder, can cause acute toxicity that presents with nausea, vomiting and diarrhea. Lithium can also cause life-threatening endocrine abnormalities, including hypercalcemia, hypernatremia, and both hypo- and hyperthyroidism. Clinical Case: A 61-year old female with hypothyroidism, bipolar disorder, hyperparathyroidism with two-gland parathyroidectomy on lithium for over 30 years presented with altered mental status. Initial labs revealed elevated creatinine 1.92 mg/dL (0.8-2.00mg/dL) compared to baseline 0.82 mg/dL, sodium 154 mg/dL (135-147 mg/dL), Corrected calcium 11.7 mg/dL (8.5-10.5 mg/dL), PTH 96 pg/mL (15-65 pg/mL), and high lithium levels 1.45 mmol/L (0.60-1.20 mmol/L). Further studies showed hypotonic polyuria with no increase in urine osmolality after desmopressin, consistent with nephrogenic diabetes insipidus. Lithium was held and she was treated with aggressive intravenous hydration with dextrose 5% water. Hypercalcemia is thought to result from increased secretion of PTH due to an increased set point at which calcium suppresses PTH release; this often resolves once lithium is stopped. Lithium can also unmask previously unrecognized mild hyperparathyroidism, and/or raise serum PTH concentrations independent of calcium levels.1 The drug interferes with the kidneys’ ability to concentrate urine in the collecting tubules by desensitizing response to antidiuretic hormone, causing diabetes insipidus. The resulting volume depletion from excessive urinary water loss in turn lead to acute kidney injury and hypernatremia.2 Hypothyroidism results from lithium-inhibited synthesis and release of thyroid hormones and decreases iodine trapping. Conclusion: Although these are infrequent complications of lithium use, they remain pertinent clinical findings to consider due to their morbidity. In this case, our patient may have avoided multiple chronic electrolyte abnormalities leading to altered mental status if lithium toxicity had been recognized earlier. References:1. García-Maldonado, Gerardo, and Rubén de Jesús Castro-García. “Endocrinological Disorders Related To The Medical Use Of Lithium. A Narrative Review”. Revista Colombiana De Psiquiatría (English Ed.), vol 48, no. 1, 2019, pp. 35-43. Elsevier BV, doi:10.1016/j.rcpeng.2018.12.005. 2. Tasci, E. “Lithium-Induced Nephrogenic Diabetes Insipidus Responsive To Desmopressin”. Acta Endocrinologica (Bucharest), vol 15, no. 2, 2019, pp. 270-271. ACTA Endocrinologica Foundation, doi:10.4183/aeb.2019.270.

scholarly journals Functional studies of twelve mutant V2 vasopressin receptors related to nephrogenic diabetes insipidus: molecular basis of a mild clinical phenotype.

1998 ◽  
Vol 9 (10) ◽  
pp. 1861-1872
Author(s):  
Y Ala ◽  
D Morin ◽  
B Mouillac ◽  
N Sabatier ◽  
R Vargas ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Three Dimensional ◽  
Urine Osmolality ◽  
Complete Loss ◽  
Loss Of Function ◽  
Hydrogen Bond Formation ◽  
Functional Studies ◽  
Three Dimensional Modeling

X-linked nephrogenic diabetes insipidus (NDI) is a rare disease with defective renal and extrarenal arginine vasopressin V2 receptor responses due to mutations in the AVPR2 gene in Xq28. To study the cause of loss of function of mutant V2 receptors, we expressed 12 mutations (N55H, L59P, L83Q, V88M, 497CC-->GG, deltaR202, I209F, 700delC, 908insT, A294P, P322H, P322S) in COS-7 cells. Eleven of these, including P322H, were characterized by a complete loss of function, but the mutation P322S demonstrated a mild clinical and in vitro phenotype. This was characterized by a late diagnosis without any growth or developmental delay and a significant increase in urine osmolality after intravenous 1-deamino[D-Arg8]AVP administration. In vitro, the P322S mutant was able to partially activate the Gs/adenylyl cyclase system in contrast to the other V2R mutants including P322H, which were completely inactive in this regard. This showed not only that Pro 322 is important for proper V2R coupling, but also that the degree of impairment is strongly dependent on the identity of the substituting amino acid. Three-dimensional modeling of the P322H and P322S mutant receptors suggested that the complete loss of function of the P322H receptor could be due, in part, to hydrogen bond formation between the His 322 side chain and the carboxyl group of Asp 85, which does not occur in the P322S receptor.

scholarly journals Partial nephrogenic diabetes insipidus associated with lithium therapy

2019 ◽  
Vol 12 (9) ◽  
pp. e231093 ◽  
Author(s):  
Eka Nandoshvili ◽  
Steve Hyer ◽  
Nikhil Johri
Keyword(s):  
Diabetes Insipidus ◽  
Affective Disorder ◽  
Water Intake ◽  
Intramuscular Injection ◽  
Nephrogenic Diabetes Insipidus ◽  
Water Deprivation ◽  
Bipolar Affective Disorder ◽  
Urine Osmolality ◽  
Urinary Concentrating Ability

A 40-year-old Caucasian man developed excessive thirst and polyuria particularly at night over the preceding 6 months. He had been taking lithium for 16 years for the treatment of bipolar affective disorder. Investigations revealed subnormal maximum urinary concentrating ability after 8 hours of water deprivation and only a borderline response of urine osmolality to exogenous desmopressin given by intramuscular injection. A plasma copeptin concentration was elevated at 23 pmol/L. These results were consistent with partial nephrogenic diabetes insipidus. He was encouraged to increase his water intake as dictated by his thirst. In addition, he received amiloride with some improvement in his symptoms. Clinicians should be aware of the risk of nephrogenic diabetes insipidus with long-term lithium use and seek confirmation by a supervised water deprivation test augmented with a baseline plasma copeptin. If increased water intake is insufficient to control symptoms, amiloride may be considered.

A Case of Drug Induced Nephrogenic Diabetes Insipidus and Hyperprolactinemia in Schizophrenia Simultaneously

2005 ◽  
Vol 20 (4) ◽  
pp. 407
Author(s):  
Ho Yoel Ryu ◽  
Mi Young Lee ◽  
Yeon Lee ◽  
Jang Hyun Koh ◽  
Mi-Jin Kim ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Drug Induced

scholarly journals Chinese Skullcap in Move Free Arthritis Supplement Causes Drug Induced Liver Injury and Pulmonary Infiltrates

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Renumathy Dhanasekaran ◽  
Victoria Owens ◽  
William Sanchez
Keyword(s):  
Liver Injury ◽  
Case Reports ◽  
Pulmonary Complications ◽  
Adverse Outcomes ◽  
Medical Community ◽  
Temporal Association ◽  
Drug Induced ◽  
Over The Counter ◽  
Drug Induced Liver Injury ◽  
Pulmonary Infiltrates

Herbal medications are being increasingly used by the American population especially for common conditions like arthritis. They have been reported to cause adverse effects, including significant hepatotoxicity, but reporting remains sporadic. We report here a patient who developed drug induced liver injury following the intake of Move Free, which is an over-the-counter arthritis supplement. We propose that Chinese skullcap, which is one of the herbal ingredients of the medication, is responsible for the adverse event. There was a strong temporal association between the intake of supplement and onset of symptoms, and also there have been a few recent case reports implicating the same component. A unique observation in our case is the occurrence of pulmonary infiltrates simultaneously with the hepatotoxicity, and this side effect has not been well documented before. Both the hepatic and pulmonary complications completely resolved over few weeks after the patient stopped taking the medication. Since these supplements are readily available over the counter, we feel that it is important to document possible adverse outcomes to raise awareness in the medical community and also among patients.

scholarly journals Case Report: A Case of Congenital Nephrogenic Diabetes Insipidus Caused by Thr273Met Mutation in Arginine Vasopressin Receptor 2

2021 ◽  
Vol 9 ◽  
Author(s):  
Li Huang ◽  
Lina Ma ◽  
Linjing Li ◽  
Jiajia Luo ◽  
Tianhong Sun
Keyword(s):  
Case Report ◽  
Specific Gravity ◽  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Clinical Symptoms ◽  
Clinical Manifestations ◽  
Tubular Dysfunction ◽  
Missense Mutations ◽  
Electrolyte Disorders ◽  
Congenital Nephrogenic Diabetes Insipidus

Congenital nephrogenic diabetes insipidus (CNDI) is a rare hereditary tubular dysfunction caused mainly by X-linked recessive inheritance of AVPR2 gene mutations. Pathogenic genes are a result of mutations in AVPR2 on chromosome Xq28 and in AQP2 on chromosome 12q13. The clinical manifestations of CNDI include polyuria, compensatory polydipsia, thirst, irritability, constipation, developmental delay, mental retardation, persistent decrease in the specific gravity of urine, dehydration, and electrolyte disorders (hypernatremia and hyperchloremia). Herein, we report a rare case of CNDI caused by an AVPR2 mutation in a 2-year-old Chinese boy who had sustained polyuria, polydipsia, and irritability for more than 20 months. Laboratory examinations showed no obvious abnormality in blood sodium and chloride levels but decreased urine osmolality and specific gravity. Imaging findings were also normal. However, genetic analysis revealed a C &gt; T transition leading to T273M missense mutations in AVPR2. We provided the boy a low-sodium diet and administered oral hydrochlorothiazide and indomethacin for 1 month, after which his clinical symptoms significantly improved. This case report suggests that CNDI is characterized by pathogenic T273M missense mutations alone and expands our understanding of the pathogenesis of CNDI.

EVIDENCE THAT THE ANTIDIURETIC SUBSTANCE IN THE PLASMA OF CHILDREN WITH NEPHROGENIC DIABETES INSIPIDUS IS ANTIDIURETIC HORMONE

PEDIATRICS ◽  
1963 ◽  
Vol 32 (3) ◽  
pp. 384-388
Author(s):  
Malcolm A. Holliday ◽  
Charles Burstin ◽  
Jean Harrah
Keyword(s):  
Diabetes Insipidus ◽  
Antidiuretic Hormone ◽  
Nephrogenic Diabetes Insipidus ◽  
Water Deprivation ◽  
Jugular Vein ◽  
Urine Osmolality ◽  
Urine Flow ◽  
Antidiuretic Activity ◽  
Antecubital Vein ◽  
Assay Technique

The antidiuretic activity in the plasma of four children with nephrogenic diabetes insipidus was measured by a rat assay technique. The evidence presented to indicate that this activity was due to antidiuretic hormone (ADH) was as follows: (a) the activity was higher in jugular vein plasma than in femoral or antecubital vein plasma, (b) it was high when the children were thirsted and decreased when they drank water, (c) it was destroyed when the plasma was incubated with thioglycollate, and (d) it was ultrafilterable, and vasopressin (Pitressin), when injected, was distributed as though it was ultrafilterable. When the children were given vasopressin, there was no change in urine flow or osmolality, but plasma antidiuretic activity was higher than it was when water deprivation led to a reduction in urine flow and an increase in urine osmolality. The inference of these findings is that ADH is secreted normally in children with nephrogenic diabetes insipidus, it is ultrafilterable, but it is not a factor in modifying urine flow in response to dehydration.

scholarly journals Nephrogenic diabetes insipidus in mice caused by deleting COOH-terminal tail of aquaporin-2

2007 ◽  
Vol 292 (5) ◽  
pp. F1334-F1344 ◽  
Author(s):  
Peijun P. Shi ◽  
Xiao R. Cao ◽  
Jing Qu ◽  
Ken A. Volk ◽  
Patricia Kirby ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Hormonal Regulation ◽  
Nephrogenic Diabetes Insipidus ◽  
Mdck Cells ◽  
Collecting Duct ◽  
Phosphorylation Site ◽  
Water Channel ◽  
Urine Osmolality ◽  
Functional Expression ◽  
Aquaporin 2

In mammals, the hormonal regulation of water homeostasis is mediated by the aquaporin-2 water channel (Aqp2) of the collecting duct (CD). Vasopressin induces redistribution of Aqp2 from intracellular vesicles to the apical membrane of CD principal cells, accompanied by increased water permeability. Mutations of AQP2 gene in humans cause both recessive and dominant nephrogenic diabetes insipidus (NDI), a disease in which the kidney is unable to concentrate urine in response to vasopressin. In this study, we generated a line of mice with the distal COOH-terminal tail of the Aqp2 deleted ( Aqp2Δ 230), including the protein kinase A phosphorylation site (S256), but still retaining the putative apical localization signal (221–229) at the COOH-terminal. Mice heterozygous for the truncation appear normal. Homozygotes are viable to adulthood, with reduced urine concentrating capacity, increased urine output, decreased urine osmolality, and increased daily water consumption. Desmopressin increased urine osmolality in wild-type mice but had no effect on Aqp2Δ 230/Δ 230 mice. Kidneys from affected mice showed CD and pelvis dilatation and papillary atrophy. By immunohistochemical and immunoblot analyses using antibody against the NH2-terminal region of the protein Aqp2Δ 230/Δ 230 mice had a markedly reduced protein abundance. Expression of the truncated protein in MDCK cells was consistent with a small amount of functional expression but no stimulation. Thus we have generated a mouse model of NDI that may be useful in studying the physiology and potential therapy of this disease.

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