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[Clinical and genetic analysis of a newborn with hypoparathyroidism, sensorineural hearing loss, and renal dysplasia syndrome].
Shao, Q, Wu, P, Lin, B, Chen, S, Liu, J, Chen, S
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics. 2022;(2):222-226
Abstract
OBJECTIVE To analyze the clinical phenotype and genetic basis for a male neonate featuring hypoparathyroidism, sensorineural hearing loss, and renal dysplasia (HDR) syndrome. METHODS The child was subjected to genome-wide copy number variation (CNVs) analysis and whole exome sequencing (WES). Clinical data of the patient was analyzed. A literature review was also carried out. RESULTS The patient, a male neonate, had presented with peculiar facial appearance, simian crease and sacrococcygeal mass. Blood test revealed hypocalcemia, hypoparathyroidism. Hearing test suggested bilateral sensorineural deafness. Doppler ultrasound showed absence of right kidney. Copy number variation sequencing revealed a 12.71 Mb deletion at 10p15.3-p13 (chr10: 105 001_12 815 001) region. WES confirmed haploinsufficiency of the GATA3 gene. With supplement of calcium and vitamin D, the condition of the child has improved. CONCLUSION The deletion of 10p15.3p13 probably underlay the HDR syndrome in this patient.
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Renal Imaging: Core Curriculum 2019.
Fried, JG, Morgan, MA
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2019;(4):552-565
Abstract
Renal imaging has become a fundamental part of clinical care for patients with kidney disease. Imaging strategies for the kidney have been evolving during the past hundred years and have been even more rapidly changing during the past couple of decades due to the development of modern computed tomographic techniques, magnetic resonance imaging, and more sophisticated ultrasonographic techniques, such as contrast-enhanced ultrasonography. Applying the correct radiologic study for the clinical situation maximizes the diagnostic accuracy of the imaging, and a judicious choice between techniques helps limit radiation dose and potential adverse events. This Core Curriculum outlines the imaging modalities currently in use in radiology departments and is divided into 3 sections: (1) a review of the development of renal imaging and an outline of modalities available to the nephrologist, (2) imaging strategies for select clinical situations, and (3) a discussion of some potential adverse events from imaging, including effects of iodinated contrast on kidney function, risks of gadolinium-based contrast agents in kidney failure, and potential risks of imaging techniques that use ionizing radiation.
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Kidney Transplantation in a Patient Lacking Cytosolic Phospholipase A2 Proves Renal Origins of Urinary PGI-M and TX-M.
Mitchell, JA, Knowles, RB, Kirkby, NS, Reed, DM, Edin, ML, White, WE, Chan, MV, Longhurst, H, Yaqoob, MM, Milne, GL, et al
Circulation research. 2018;(4):555-559
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Abstract
RATIONALE The balance between vascular prostacyclin, which is antithrombotic, and platelet thromboxane A2, which is prothrombotic, is fundamental to cardiovascular health. Prostacyclin and thromboxane A2 are formed after the concerted actions of cPLA2α (cytosolic phospholipase A2) and COX (cyclooxygenase). Urinary 2,3-dinor-6-keto-PGF1α (PGI-M) and 11-dehydro-TXB2 (TX-M) have been taken as biomarkers of prostacyclin and thromboxane A2 formation within the circulation and used to explain COX biology and patient phenotypes, despite concerns that urinary PGI-M and TX-M originate in the kidney. OBJECTIVE We report data from a remarkable patient carrying an extremely rare genetic mutation in cPLA2α, causing almost complete loss of prostacyclin and thromboxane A2, who was transplanted with a normal kidney resulting in an experimental scenario of whole-body cPLA2α knockout, kidney-specific knockin. By studying this patient, we can determine definitively the contribution of the kidney to the productions of PGI-M and TX-M and test their validity as markers of prostacyclin and thromboxane A2 in the circulation. METHODS AND RESULTS Metabolites were measured using liquid chromatography-tandem mass spectrometry. Endothelial cells were grown from blood progenitors. Before kidney transplantation, the patient's endothelial cells and platelets released negligible levels of prostacyclin (measured as 6-keto-prostaglandin F1α) and thromboxane A2 (measured as TXB2), respectively. Likewise, the urinary levels of PGI-M and TX-M were very low. After transplantation and the establishment of normal renal function, the levels of PGI-M and TX-M in the patient's urine rose to within normal ranges, whereas endothelial production of prostacyclin and platelet production of thromboxane A2 remained negligible. CONCLUSIONS These data show that PGI-M and TX-M can be derived exclusively from the kidney without contribution from prostacyclin made by endothelial cells or thromboxane A2 by platelets in the general circulation. Previous work relying on urinary metabolites of prostacyclin and thromboxane A2 as markers of whole-body endothelial and platelet function now requires reevaluation.
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Clinical and mutational spectrum of hypoparathyroidism, deafness and renal dysplasia syndrome.
Belge, H, Dahan, K, Cambier, JF, Benoit, V, Morelle, J, Bloch, J, Vanhille, P, Pirson, Y, Demoulin, N
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2017;(5):830-837
Abstract
BACKGROUND Hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome is a rare autosomal dominant disorder, secondary to mutations in the GATA-3 gene. Due to its wide range of penetrance and expressivity, the disease may not always be recognized. We herein describe clinical and genetic features of patients with HDR syndrome, highlighting diagnostic clues. METHODS Medical records of eight patients from five unrelated families exhibiting GATA-3 mutations were reviewed retrospectively, in conjunction with all previously reported cases. RESULTS HDR syndrome was diagnosed in eight patients between the ages of 18 and 60 years. Sensorineural deafness was consistently diagnosed, ranging from clinical hearing loss since infancy in seven patients to deafness detected only by audiometry in adulthood in one single patient. Hypoparathyroidism was present in six patients (with hypocalcaemia and inaugural seizures in two out of six). Renal abnormalities observed in six patients were diverse and of dysplastic nature. Three patients displayed nephrotic-range proteinuria and reached end-stage renal disease (ESRD) between the ages of 19 and 61 years, whilst lesions of focal and segmental glomerulosclerosis were histologically demonstrated in one of them. Interestingly, phenotype severity differed significantly between a mother and son within one family. Five new mutations of GATA-3 were identified, including three missense mutations affecting zinc finger motifs [NM_001002295.1: c.856A>G (p.N286D) and c.1017C>G (p.C339W)] or the conserved linker region [c.896G>A (p.R299G)], and two splicing mutations (c.924+4_924+19del and c.1051-2A>G). Review of 115 previously reported cases of GATA-3 mutations showed hypoparathyroidism and deafness in 95% of patients, and renal abnormalities in only 60%. Overall, 10% of patients had reached ESRD. CONCLUSIONS We herein expand the clinical and mutational spectrum of HDR syndrome, illustrating considerable inter- and intrafamilial phenotypic variability. Diagnosis of HDR should be considered in any patient with hypoparathyroidism and deafness, whether associated with renal abnormalities or not. HDR diagnosis is established through identification of a mutation in the GATA-3 gene.
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Disorders of fatty acid oxidation and autosomal recessive polycystic kidney disease-different clinical entities and comparable perinatal renal abnormalities.
Hackl, A, Mehler, K, Gottschalk, I, Vierzig, A, Eydam, M, Hauke, J, Beck, BB, Liebau, MC, Ensenauer, R, Weber, LT, et al
Pediatric nephrology (Berlin, Germany). 2017;(5):791-800
Abstract
BACKGROUND Differential diagnosis of prenatally detected hyperechogenic and enlarged kidneys can be challenging as there is a broad phenotypic overlap between several rare genetic and non-genetic disorders. Metabolic diseases are among the rarest underlying disorders, but they demand particular attention as their prognosis and postnatal management differ from those of other diseases. METHODS We report two cases of cystic, hyperechogenic and enlarged kidneys detected on prenatal ultrasound images, resulting in the suspected diagnosis of autosomal recessive polycystic kidney disease (ARPKD). Postnatal clinical course and work-up, however, revealed early, neonatal forms of disorders of fatty acid oxidation (DFAO) in both cases, namely, glutaric acidemia type II, based on identification of the novel, homozygous splice-site mutation c.1117-2A > G in the ETFDH gene, in one case and carnitine palmitoyltransferase II deficiency in the other case. RESULTS Review of pre- and postnatal sonographic findings resulted in the identification of some important differences that might help to differentiate DFAO from ARPKD. In DFAO, kidneys are enlarged to a milder degree than in ARPKD, and the cysts are located ubiquitously, including also in the cortex and the subcapsular area. Interestingly, recent studies have pointed to a switch in metabolic homeostasis, referred to as the Warburg effect (aerobic glycolysis), as one of the underlying mechanisms of cell proliferation and cyst formation in cystic kidney disease. DFAO are characterized by the inhibition of oxidative phosphorylation, resulting in aerobic glycolysis, and thus they do resemble the Warburg effect. We therefore speculate that this inhibition might be one of the pathomechanisms of renal hyperproliferation and cyst formation in DFAO analogous to the reported findings in ARPKD. CONCLUSIONS Neonatal forms of DFAO can be differentially diagnosed in neonates with cystic or hyperechogenic kidneys and necessitate immediate biochemical work-up to provide early metabolic management.
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Simultaneous detection of Gaucher's disease and renal involvement of non-Hodgkin's lymphoma: the first Asian case report and a review of literature.
Kim, MJ, Suh, JT, Lee, HJ, Lee, WI, Moon, A, Lee, J, Kang, SH, Cho, EH, Oh, SH, Baek, SK, et al
Annals of clinical and laboratory science. 2012;(3):293-301
Abstract
Gaucher's disease (GD) is a rare autosomal recessive (AR) disorder characterized by a deficiency of glucocerebrosidase (glucosylceramidase, acid β-glucosidase). This enzyme deficiency results in an accumulation of sphingolipids in the cells of GD patients, which may contribute to the dysregulation of the immune system, B-cell dysfunction and expression of specific cytokines such as interleukin (IL) -1, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF). Accumulated substrate may directly affect the patient's immunity and pose a higher risk for cancer, especially hematologic malignancies. However, recent large-scale studies suggest that the relative risks of GD and hematologic malignancies are not statistically significant and, therefore, their association with each other remains controversial. In this report, we present the first Asian GD case where the patient was simultaneously diagnosed with a non-Hodgkin's lymphoma. A renal biopsy confirmed that the patient had diffuse large B-cell lymphoma (DLBCL). A bone marrow study during lymphoma staging revealed Gaucher cells with abundant fibrillary, blue-gray cytoplasm and a wrinkled, tissue paper-like appearance. Subsequently, an acid β-glucosidase (GbA) gene mutation study demonstrating two heterozygote mutations, G202R (c.721G>A; p.G241R), a known pathogenic mutation, and a novel mutation R277C (c.946C>T; p.R316C) prompted the diagnosis of GD. Previous case reports have demonstrated concurrent GD and lymphoma in type 1 GD patients, with 40% of patients diagnosed with GD when a lymphoma is detected during disease evaluation. In Korea, GD cases with the G202R gene mutation have been reported in neuropathic patients with a very low frequency. To our knowledge, this case represents the first observation of the G202R mutation in a type 1 GD patient associated with lymphoma. Furthermore, this report is the first patient with DLBCL with kidney involvement along with GD.
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[Renal side effects of long-term lithium therapy].
Ibbeken, C, Becker, JU, Baumgärtel, MW
Deutsche medizinische Wochenschrift (1946). 2012;(4):143-8
Abstract
Lithium is widely used in the treatment of bipolar disorders. Long-term administration of lithium often leads to side effects concerning the subjects: nephrology, endocrinology and surgery. This review emphasizes nephrotoxicity.Lithium treatment may disturb responsiveness to antidiuretic hormone (ADH), causing a nephrogenic diabetes insipidus. Furthermore long-term lithium therapy may trigger hyperparathyreoidism with hypercalcemia and chronic interstitial nephritis with development of microcysts. Long-term patients have an increased risk to develop impaired renal function. Lithium-induced endstage renal disease is rare. Termination of lithium treatment may decrease the risk of progression.To ensure security of lithium treatment regular controls of urine osmolarity, lithium-, creatinine- , thyroid stimulating hormone- and calcium-levels are essential. Patients with decreased renal function should be referred to a specialist early.
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Acute lymphoblastic leukemia complicated by acute renal failure: a case report and review of the literature.
Zhou, Y, Tang, Z, Liu, ZH, Li, LS
Clinical nephrology. 2010;(4):321-5
Abstract
The patient, a previously healthy woman, presenting with acute renal failure and anemia, was admitted to our hospital. Her serum creatinine (Scr) had increased from 0.79 - 2.69 mg/dl over three days and hemoglobin had decreased from 12.1 - 7.8 g/dl over 4 weeks. Mild compression fracture and degeneration of the lumbar vertebra and skull were observed in X-ray. The renal biopsy showed acute proximal tubular lesions induced by multiple calcium deposition. A bone marrow biopsy showed that primitive lymphocyte was up to 92.5%. After making a diagnosis of acute lymphoblastic leukemia complicated with acute kidney injury induced by hypercalcemia, CRRT (continued renal replacement therapy) and chemotherapy were used immediately. Ten days later, the blood calcium had gradually decreased from 3.88 to normal range (1.8 mmol/l) and the renal function was back to normal (Scr 0.93 mg/dl). This unusual case shows that a patient who has a syndrome of acute renal failure, electrolyte disturbances, anemia, and elevated LDH needs bone marrow puncture to eliminate renal injury caused by hematologic diseases.
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Misapplications of commonly used kidney equations: renal physiology in practice.
Nguyen, MT, Maynard, SE, Kimmel, PL
Clinical journal of the American Society of Nephrology : CJASN. 2009;(3):528-34
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Equations for estimating GFR, quantifying urinary protein excretion, and assessing renal sodium handling are widely used in routine nephrology and general medical and surgical practice. If these equations are applied in circumstances inconsistent with the clinical situations for or extrapolated beyond the limits in which they were validated, clinicians can come to erroneous conclusions, which could be detrimental for patient care. This review uses clinical vignettes to demonstrate some of the common pitfalls that clinicians may encounter in the use of these equations and considers the physiologic principles underlying their use. Equations for assessing aspects of renal function should only be used in specific clinical situations, if the underlying assumptions regarding their calculations and values are satisfied.
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Acetaminophen-induced nephrotoxicity: pathophysiology, clinical manifestations, and management.
Mazer, M, Perrone, J
Journal of medical toxicology : official journal of the American College of Medical Toxicology. 2008;(1):2-6
Abstract
UNLABELLED Acetaminophen-induced liver necrosis has been studied extensively, but the extrahepatic manifestations of acetaminophen toxicity are currently not described well in the literature. Renal insufficiency occurs in approximately 1-2% of patients with acetaminophen overdose. The pathophysiology of renal toxicity in acetaminophen poisoning has been attributed to cytochrome P-450 mixed function oxidase isoenzymes present in the kidney, although other mechanisms have been elucidated, including the role of prostaglandin synthetase and N-deacetylase enzymes. Paradoxically, glutathione is considered an important element in the detoxification of acetaminophen and its metabolites; however, its conjugates have been implicated in the formation of nephrotoxic compounds. Acetaminophen-induced renal failure becomes evident after hepatotoxicity in most cases, but can be differentiated from the hepatorenal syndrome, which may complicate fulminant hepatic failure. The role of N-acetylcysteine therapy in the setting of acetaminophen-induced renal failure is unclear. This review will focus on the pathophysiology, clinical features, and management of renal insufficiency in the setting of acute acetaminophen toxicity. CASE A 47-year-old female was found lethargic at home and brought by ambulance to an emergency department. History from family members suggested an inadvertent acetaminophen overdose, and she had last been seen a few hours earlier. She reportedly ingested 18 tablets of 500 mg acetaminophen (APAP) over the previous two days because she had run out of her prescription pain medication. Her past medical history was significant for fibromyalgia, arthritis, and a prior gastric bypass procedure. She had no history of alcohol abuse or renal insufficiency. She was lethargic. Vital signs: BP 128/96 mmHg, pulse 112/min, respirations 32/min; pulse oximetry 98% on 2L nasal cannula oxygen. Laboratory studies: BUN 9 mg/dL, creatinine 0.9 mg/dl, acetaminophen 12 mcg/mL, AST 5409 u/L and ALT 1085 u/L. A urinalysis was negative for blood with trace protein and ketones. A urine drug screen was positive for marijuana and opioid metabolites. At the initial hospital, she was treated with N-acetylcysteine (NAC) orally. Subsequently, she developed fulminant hepatic failure with elevated transaminases, hypoglycemia, and coagulopathy (Tables 1A and 1B). She was transferred to our facility two days after initial presentation for liver transplant evaluation. At that time, her APAP level was 2.0 mg/L. Oral NAC therapy was continued after transfer. The patient's liver function subsequently improved and she ultimately did not require transplantation. She did develop acute renal failure during the course of her hospitalization, with a creatinine of 2.3 mg/dL on transfer, which increased to 8.1 mg/dL nine days later (approximately 11-13 days post-ingestion). Medical toxicology was consulted by the intensive care unit team to address whether this was acetaminophen-induced renal failure and if there was a role for NAC in this setting.