Uremic patients may have a variety of organ involvement, however, the precise causality may be impossible to determine in some cases because the symptoms of uremia are also associated with other diseases. With an emphasis on the elusive nature of uremia, we herein describe a 53-year-old man with preexisting renal impairment who developed acute pericarditis with deterioration of his renal function. Hemodialysis was immediately initiated on the presumption of uremia, however, articular symptoms emerged approximately a month later and led to a final diagnosis of rheumatoid arthritis, followed by successful withdrawal of hemodialysis.
A transdermal patch formulation of a non-steroidal anti-inflammatory drug (NSAID) used by a 44-year-old man resulted in acute interstitial nephritis and acute tubular injury. This patient also had a history of mild kidney dysfunction and osteoporosis. The NSAID patch had been prescribed after a traffic accident. He was also receiving a vitamin D analog and taking over-the-counter calcium supplements. Two months later, renal dysfunction and hypercalcemia were discovered. A renal biopsy showed acute interstitial nephritis and acute tubular injury. Once these agents were withdrawn, the renal function recovered. This is the first reported occurrence of biopsy-proven acute interstitial nephritis attributable to NSAID patch usage.
To investigate the efficacy of effluent biomarkers for peritoneal deterioration with functional decline in peritoneal dialysis (PD).From January 2005 to March 2013, the subjects included 218 PD patients with end-stage renal disease at 18 centers. Matrix metalloproteinase-2 (MMP-2), interleukin-6 (IL-6), hyaluronan, and cancer antigen 125 (CA125) in peritoneal effluent were quantified with enzyme-linked immunosorbent assay. Peritoneal solute transport rate was assessed by peritoneal equilibration test (PET) to estimate peritoneal deterioration.The ratio of the effluent level of creatinine (Cr) obtained 4 h after injection (D) to that of plasma was correlated with the effluent levels of MMP-2 (ρ = 0.74, P < 0.001), IL-6 (ρ = 0.46, P < 0.001), and hyaluronan (ρ = 0.27, P < 0.001), but not CA125 (ρ = 0.13, P = 0.051). The area under receiver operating characteristic curve for the effluent levels of MMP-2, IL-6, and hyaluronan against high PET category were 0.90, 0.78, 0.62, and 0.51, respectively. No patient developed new-onset encapsulating peritoneal sclerosis for at least 1.5 years after peritoneal effluent sampling.The effluent MMP-2 level most closely reflected peritoneal solute transport rate. MMP-2 can be a reliable indicator of peritoneal deterioration with functional decline.
Background: Malignant hypertension is a disease characterized by severe hypertension and multi-organ damage. Although mortality and renal prognosis have improved with antihypertensive therapy, progression to end-stage renal disease remains a leading cause of morbidity and mortality. Case presentation: A 37-year-old man with a history of untreated hypertension and proteinuria was referred to our hospital with complaints of right paralysis. He was diagnosed with left putaminal hemorrhage and treated with conservative blood pressure reduction management. He was also complicated with severe hypertension (blood pressure 231/146 mmHg), acute renal failure (BUN 39 mg/dl, serum creatinine 4.01 mg/dl, urinary protein 2.848 g/gCre), and heart failure with preserved ejection fraction (BNP 373 pg/ml). Initial evaluation demonstrated hyperreninemia (32.6 ng/ml/hr) with hyperaldosteronism (125 pg/ml), consistent with malignant hypertension. Secondary hypertension, such as primary aldosteronism, Cushing's syndrome, pheochromocytoma, and renal artery stenosis was excluded by further examination. His renal size was mildly atrophic assessed by CT scan, suggesting a history of chronic kidney disease. At first, we gradually decreased blood pressure with antihypertensive agents except for angiotensin-converting enzyme (ACE) inhibitor and angiotensin receptor blockade (ARB) so as not to induce exacerbation of renal function via glomerular ischemia. In the long-term, he was treated to achieve a tight blood pressure control to systolic blood pressure of 100–110 mmHg with the combination of ACE inhibitor, calcium channel blocker, and alpha/beta blocker. Although his clinical course showed gradual recovery of renal function, our conservative approach successfully induced renal function recovery over six months of follow-up (BUN 27 mg/dl, serum creatinine 2.26 mg/dl, urinary protein 0.154 g/gCre). Discussion: Previous reports suggest that malignant nephrosclerosis may recover slowly if the blood pressure is tightly controlled during the follow-up. From a long-term perspective, tight blood pressure control with inhibition of the renin-angiotensin-aldosterone system, which is a critical factor of the pathogenesis in malignant hypertension, may provide beneficial effects on the renal prognosis of malignant hypertension.
We examined whether fingolimod (FTY720), an S1PR (sphingosine-1-phosphate receptor) modulator, has beneficial or harmful effects on mineralocorticoid/salt-induced renal injury. Uninephrectomized rats on 0.9% NaCl/0.3% KCl drinking solution were randomly divided into control, control+FTY720, deoxycorticosterone acetate (DOCA), and DOCA+FTY720 groups and administered vehicle, vehicle+FTY720, DOCA+vehicle, and DOCA+FTY720 for 4 weeks, respectively. Only the DOCA+FTY720 group had reduced survival rates and showed hemolysis because of intravascular mechanical fragmentation of erythrocytes and thrombocytopenia. Both the DOCA+FTY720 and DOCA groups developed malignant hypertension, which was more severe in the DOCA+FTY720 group. In the DOCA+FTY720 group only, thrombotic microangiopathy involving severe renal arteriole endothelial cell injury was observed and was characterized by fibrinoid necrosis and onion-skin lesions in arterioles. There were fewer circulating endothelial progenitor cells in the DOCA+FTY720 group but more in the DOCA group compared with the control group. Expression levels of VEGF (vascular endothelial growth factor), S1PR1, and S1PR3 in renal arteriole endothelial cells were significantly greater in the DOCA+FTY720 and DOCA groups compared with the control group, with levels being similar between the 2 groups. Expression levels of endothelial nitric oxide synthase in renal arteriole endothelial cells were significantly lower in the DOCA+FTY720 group only. The control+FTY720 group showed reduced circulating endothelial progenitor cells but no significant functional or pathological changes in kidneys or changes in blood pressure. Exposure of uninephrectomized rats to DOCA/salt+FTY720 for 4 weeks induced renal arteriolar endothelial cell injury, resulting in the development of thrombotic microangiopathy. Consideration of this possibility is recommended when prescribing FTY720.
Epidermal growth factor (EGF), an essential factor for the proliferation and survival of renal tubular cells, is expressed by distal tubules and normally excreted via urine. Previous studies in rats demonstrated that acute tubular injury reduces urinary EGF levels. However, it is unclear whether urinary EGF is a suitable monitoring marker of tubular repair status after acute kidney injury (AKI) in humans. To address this question, we measured serum and urinary EGF in patients with AKI (n = 99) using ELISA and investigated whether urinary EGF levels were associated with the severity of tubular injury and renal prognosis. Urinary EGF was abundant in healthy controls but showed a significant decrease in AKI patients (14,522 ± 2190 pg/mL vs. 3201 ± 459.7 pg/mL, p < 0.05). The urinary EGF level in patients with renal AKI was notably lower than that in patients with pre-renal AKI. Furthermore, the urinary EGF level in patients with AKI stage 3 was significantly lower than that in patients with AKI stage 1. Urinary EGF levels were negatively correlated with urinary β-2MG and serum creatinine levels but positively correlated with hemoglobin levels and eGFR. Urinary EGF was not significantly correlated with urinary NAG, α-1MG, L-FABP, NGAL, KIM-1, or urinary protein concentrations. No significant correlation was observed between serum and urinary EGF levels, suggesting that urinary EGF is derived from the renal tubules rather than the blood. In living renal transplantation donors, the urinary EGF/Cr ratio was approximately half the preoperative urinary EGF/Cr ratio after unilateral nephrectomy. Collectively, these data suggest that urinary EGF is a suitable noninvasive indicator of not only the volume of functional normal renal tubules but also the status of tubular repair after AKI.
Background. Peritoneal mesothelial cells play an important role in peritoneal dialysis and are often exposed to dialysis fluid containing high glucose levels. Loss of peritoneal function is a major complication associated with long-term peritoneal dialysis. In this study, we hypothesized that high glucose levels induce apoptosis, and that insulin attenuates this apoptosis in peritoneal mesothelial cells. To clarify this hypothesis, we examined the effects of insulin on the phosphatidylinositol 3-kinase/Akt signaling pathway and apoptosis in rat peritoneal mesothelial cells.
Deep venous thrombosis (DVT) in the upper extremities is a rare but important clinical illness, which leads to severe complications such as pulmonary embolism. Unlike DVT in the lower extremities, which is mainly induced by a hypercoagulable state, DVT in the upper extremities is usually caused by mechanical obstruction or anatomical stenosis in the venous system. We herein report a case in which DVT developed in the left upper limb during treatment of nephrotic syndrome. This is the first case report of upper-extremity DVT in association with nephrotic syndrome in the literature. Our patient was a 56-year-old male with nephrotic syndrome due to idiopathic membranous nephropathy who was treated with 40 mg/day of prednisolone. During corticosteroid therapy, he developed a swelling of the left upper limb. Computed tomography revealed thrombi in the left internal jugular vein and the left subclavian vein without anatomical abnormalities in his venous system. Thus, he was diagnosed with DVT of the upper extremities. After the initiation of warfarin treatment and subsequent regression of nephrotic syndrome, the swelling disappeared and the thrombi significantly diminished. DVT should be considered when upper-extremity edema is observed in patients with nephrotic syndrome.
Renal biopsy is one of the pivotal diagnostic tools used in the field of nephrology. A morphological analysis of the kidney may also be of value for the overall management of patients with diabetic nephropathy. However, the indications for renal biopsy differ considerably among nephrologists, and no global consensus regarding performing this procedure among diabetic patients with various renal manifestations has yet been achieved. In this report, we would like to describe our serendipitous experience with a male type 2 diabetic patient presenting with nephrotic syndrome complicated by concurrent gastric carcinoma. We also discuss several conundrums that arose in the current case, which had an impact on our diagnostic and therapeutic decisions.
