Iron chelators reverse organ damage in type 4B hereditary hemochromatosis: Case reports.

RATIONALE: Hereditary hemochromatosis (HH) is a hereditary disorder of iron metabolism. It is classified into 4 main types depending on the underlying genetic mutation: human hemochromatosis protein (HFE) (type 1), hemojuvelin (HJV) (type 2A), HAMP (type 2B), transferrin receptor-2 (TFER2) (type 3), and ferroportin (type 4). Type 4 HH is divided into 2 subtypes according to different mutations: type 4A (classical ferroportin disease) and type 4B (non-classical ferroportin disease). Type 4B HH is a rare autosomal dominant disease that results from mutations in the Solute Carrier Family 40 member 1 (SLC40A1) gene, which encodes the iron transport protein ferroportin. PATIENT CONCERNS: Here we report 2 elderly Chinese Han men, who were brothers, presented with liver cirrhosis, diabetes mellitus, skin hyperpigmentation, hyperferritinaemia as well as high transferrin saturation. DIAGNOSIS: Subsequent genetic analyses identified a heterozygous mutation (p. Cys326Tyr) in the SLC40A1 gene in both patients. INTERVENTIONS: We treated the patient with iron chelator and followed up for 3 years. OUTCOMES: Iron chelator helped to reduce the serum ferritin and improve the condition of target organs, including skin, pancreas, liver as well as pituitary. LESSONS: Type 4B HH is rare but usually tends to cause multiple organ dysfunction and even death. For those patients who have difficulty tolerating phlebotomy, iron chelator might be a good alternative.

Failure to place a tunneled hemodialysis catheter due to malformation of right internal jugular vein draining to subclavian vein.

The right internal jugular vein (IJV) is an important access site for hemodialysis catheterization. Venous cannulation failure is usually caused by central venous stenosis and is rarely related to vessel malformation. We herein present a case of failure to place a tunneled hemodialysis catheter into the right IJV. The patient had an arteriovenous fistula in the right arm with inadequate flow and a history of multiple central venous catheterizations. The guidewire was repeatedly misplaced into the right subclavian vein (SV) regardless of the technique used. Computed tomography venography revealed that the inferior segment of the right IJV drained into the ipsilateral SV. To the best of our knowledge, this is the first report of catheterization failure due to abnormal drainage of the right IJV into the ipsilateral SV.

[Temporally Relationship between Renal Local Clock System and Circadian Rhythm of the Water Electrolyte Excretion].

OBJECTIVE: To investigate the relationship of the circadian rhythm of the urine volume and urine electrolytes excretion rate and the daily expression pattern of the clock genes and clock-controlled genes with the water electrolyte transportation circadian pattern in rat kidneys. METHODS: Male adult SD rats were exposed to in a light:dark (12:12) cycles. We collected two period urine from zeitgeber time (ZT)00:00-ZT12:00 (light time,rest period) and ZT12:00-24:00 (dark time,activity period) and then compared the urinary excretion rates of volume, sodium, potassium, and chloride at light time with those at dark time. Rats were sacrificed every 4 hours throughout a 24-hour day-night cycle. Circadian clock gene CLOCK, BMAL1,Per1,Per2,Cry1,Cry2 and kidney specific clock-controlled gene NHE3,αENaC、NCC,Ptges,V1aR,V2R expression were profiled by real-time quantitative polymerase chain reaction. Data were analysed by a partial Fourier analysis and a stepwise regression technique. RESULTS: Urine volume and urine potassium excretion rate displayed high level at dark time and low at light time in SD rats (P<0.05),and urine sodium and chloride excretion rate also showed the trend(P>0.05).Clock gene CLOCK,BMAL1,Per1,Per2,Cry1,Cry2(P<0.05)and kidney specific clock-controlled gene NHE3, αENaC, NCC, Ptges, V1aR, V2R (P<0.05)mRNA expression showed circadian pattern,and the peak times of the genes were in the dark time. CONCLUSION: Urine volume and urine electrolyte excretion rate which displayed circadian pattern were temporally coupled with the rhythm of expression of clock and clock-controlled genes associated with water electrolyte transportation in rats kidney.

A novel homozygous GLUT9 mutation cause recurrent exercise-induced acute renal failure and posterior reversible encephalopathy syndrome.

Renal hypouricemia (RHU) is an autosomal recessive hereditary disease characterized by impaired renal urate reabsorption and subsequent profound hypouricemia. There are two types of RHU, type 1 and type 2, caused by the loss-of-function mutation of SLC22A12 and SLC2A9 genes, respectively. RHU predisposes affected people to exercise-induced acute renal failure (EIARF), posterior reversible encephalopathy syndrome (PRES) and nephrolithiasis. A Chinese patient had experienced three episodes of EIARF and one episode of PRES. The investigations showed profound hypouricemia and significantly increased renal excretion of UA. Cranial magnetic resonance imaging showed communicating hydrocephalus. Renal biopsy displayed interlobular artery intimal thickening with reduction of lumen and acute tubulointerstitial injury. The mutational analysis revealed a homozygous splice-site mutation in the SLC2A9 gene encoding glucose transporter 9. The patient was diagnosed as RHU type 2 caused by a loss-of-function mutation of the SLC2A9 gene. Consequently, he was strictly prohibited from strenuous exercise. During the 5-year follow-up, EIARF and PRES never recurred. Strenuous exercise may induce systemic (including renal and cerebrovascular) vasoconstriction eventually resulting in EIARF and PRES in patients with RHU. To our knowledge, this is the first report of a homozygous splice-site mutation in the SLC2A9 gene, renal arteriolar chronic lesion, concurrence of RHU and communicating hydrocephalus.

Fanconi syndrome caused by low-dose adefovir dipivoxil.

Adefovir dipivoxil (ADV) at a low-dose (10 mg daily), which was previously considered not nephrotoxic, was reported to have induced acquired Fanconi syndrome (FS). We report one 64-year-old Chinese woman and 2 Chinese men (ages 45 and 63 years) with bone pain, and/or muscle weakness on ADV therapy were diagnosed with low-dose ADV-induced FS. The serum phosphate normalized, or nearly normalized in the first and second patients after changing ADV to entecavir with, or without phosphate supplement, but did not improve significantly in the third patient after changing ADV to tenofovir, even though he was supplied with a higher dose of phosphate. Low-dose ADV-related FS is not rare in the Asian population. Regular monitoring of urine and serum phosphate is necessary during therapy with ADV. Prognosis was favorable, however, tenofovir is not a suitable replacement for ADV.

[Effect of coicis semen oil on renal interstitial fibrosis in rats with unilateral urethral obstruction].

OBJECTIVE: To study the effect and mechanism of Coicis Semen oil (Kanglaite injection, KLT) on renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO). METHOD: Fifty-four male SD rats were randomly divided into 3 groups, 6 in each group, the sham operated group, the model group, and the KLT group. Renal interstitial fibrosis model was established in rats by UUO. After administration of KLT (15 mL x kg(-1) x d(-1)) for 3, 7 and 14 days, the dynamic histological changes of renal interstitial tissues were observed and renal damage including tubular impairment and interstitial fibrosis were quantified on HE and Masson stained tissue sections. The expression of alpha-smooth muscle actin (alpha-SMA) and transforming growth factor-beta1 (TGF-beta1) were measured by immunohistochemistry staining sections. The protein expression of p-Smad2 and Smad7 were detected by Western blot respectively. RESULT: The degree of tubular damage in KLT group was much lower than that in UUO group (P < 0.05). The expression of alpha-SMA and TGF-beta1 was decreased in both UUO group and KLT group, while it was significantly lower in KLT group at every time point. The protein expression of p-Smad2 was obviously decreased while the protein expressions of Smad7 was obviously increased in KLT group, compared with the UUO group (P < 0.05). CONCLUSION: Coicis Semen oil could attenuate the tubulo-interstitial fibrosis, probable by intervening the TGF-beta/Smads signal transduction pathway of UUO rats.

[The relationship between urinary albumin excretion and serum uric acid in general population].

OBJECTIVE: To investigate the relationship between the urinary albumin excretion (UAE) and serum uric acid in general population. METHODS: The study participants were derived from the epidemiological study on the association of metabolic syndrome and chronic kidney disease (CKD) in Pinggu district, Beijing. A total of 992 participants (463 men and 529 women) aged from 30 to 75 years were enrolled in this study. For each participant, UAE, serum uric acid, serum creatinine, and serum lipids were detected and other potential risk factors for CKD were surveyed. RESULTS: (1) The frequencies of microalbuminuria, macroalbuminuria and hyperuricemia were 12.9%, 1.8% and 4.3% respectively. The persons with hyperuricemia had significantly higher frequency of albuminuria than those without hyperuricemia (37.2% vs 13.7%, P < 0.01). (2) The participants were divided according to the quartiles (25%, 50%, 75%) of serum uric acid level, and the frequencies of albuminuria in males were 13.2%, 13.9%, 17.2% and 25.4%, while those in females were 8.4%, 6.2%, 9.6% and 24.8%. (3) Multivariate logistic regression analysis showed, hyperuricemia was significantly associated with albuminuria in females (OR = 2.31, 95%CI 1.15-4.68; P = 0.02), but not in males. If the persons with reduced renal function were excluded, similar result still could be gained. CONCLUSIONS: The prevalence of albuminuria increases gradually with uric acid elevation. Serum uric acid is an independent risk factor of elevated UAE, especially in females.

[Clinical analysis of anti glomerular basement membrane disease with normal renal function].

OBJECTIVE: To investigate the clinical and pathologic characteristics of anti-glomerular basement membrane(GBM) disease with normal renal function. METHODS: The clinical and pathologic data of 6 patients with anti-GBM disease and normal renal function in Peking Union Medical College Hospital were reviewed retrospectively. Furthermore, 29 patients with anti-GBM disease and impaired renal function in the same period in the same hospital were enrolled as the control group. Factors that may influence the prognosis were analyzed. RESULTS: Six (17.1%) of all 35 patients maintained normal renal function for 12-133 months during follow-up. Five patients had microhematuria and proteinuria, one had pulmonary hemorrhage only, and three manifested as Goodpasture syndrome. Renal biopsies from 4 patients revealed linear deposition of IgG 2+-3+ along the glomerular capillary walls by immunofluorescence. As shown by normal light microscopy, mild mesangial proliferation and crescentic glomerulonephritis with a large amount of fibrinoid necrosis of glomerular capillary walls were observed in different patients; however, most pathological changes were mild. Five of these six patients were treated with immunosuppressive drugs and/or plasma exchange. Compared with the control group, the 6 patients with normal renal function had significantly higher hemoglobin[(77.97±20.62 vs.(99.67±19.80 g/L P=0.024], lower titers of anti-GBM antibody[(224.34 ± 145.79 vs.(80.23 ± 85.73 EU/ml P=0.027], and lower ratio of glomeruli with crescents[(0.58±0.29 vs.(0.17±0.27 ,P=0.005]. These 6 patients with normal renal function were followed up for 12-133 months, among whom 4 patients achieved complete remission and 2 had mild proteinuria and microhematuria. CONCLUSION: Anti-GBM disease with normal renal function is not uncommon. Most patients have mild pathologic changes and good prognosis.