Isolated massive histiocytes renal interstitial infiltration: a case report of an unexpected cause of acute kidney injury in a kidney transplant recipient.

BACKGROUND: Acute kidney injury is a frequent cause of hospital readmission in kidney transplant recipients (KTR), usually associated with infections and graft rejection. Herein, we report a case of an unusual cause of acute kidney injury in a KTR (massive histiocytes renal interstitial infiltration). CASE PRESENTATION: A 40-year-old woman was submitted to a second kidney transplant. One year after surgery, she presented asthenia, myalgia, and fever, haemoglobin 6.1 g/dL; neutrophils: 1.3 × 109/µL; platelets: 143 × 109/µL; blood creatinine 11.8 mg/dL, requiring dialysis. A kidney biopsy revealed diffuse histiocytic infiltration, which was assumed due to dysregulated immunological activation triggered by infections. The patient had multiple infections, including cytomegalovirus infection (CMV), aspergillosis, bacteraemia, and urinary tract infections, which could trigger the immune response. Haemophagocytic lymphohistiocytosis (HLH) was ruled out. The present case highlights the occurrence of isolated massive renal interstitial infiltration of histiocytes that does not meet the criteria for HLH or other related pathologies. CONCLUSIONS: Renal histiocyte activation and infiltration may have been initiated by an immunological mechanism similar to what occurs in HLH and infectious processes. The present case highlights the occurrence of isolated massive renal interstitial infiltration of histiocytes that does not meet the criteria for HLH or other related pathologies.

Calcitriol Reduces the Inflammation, Endothelial Damage and Oxidative Stress in AKI Caused by Cisplatin.

Cisplatin treatment is one of the most commonly used treatments for patients with cancer. However, thirty percent of patients treated with cisplatin develop acute kidney injury (AKI). Several studies have demonstrated the effect of bioactive vitamin D or calcitriol on the inflammatory process and endothelial injury, essential events that contribute to changes in renal function and structure caused by cisplatin (CP). This study explored the effects of calcitriol administration on proximal tubular injury, oxidative stress, inflammation and vascular injury observed in CP-induced AKI. Male Wistar Hannover rats were pretreated with calcitriol (6 ng/day) or vehicle (0.9% NaCl). The treatment started two weeks before i.p. administration of CP or saline and was maintained for another five days after the injections. On the fifth day after the injections, urine, plasma and renal tissue samples were collected to evaluate renal function and structure. The animals of the CP group had increased plasma levels of creatinine and of fractional sodium excretion and decreased glomerular filtration rates. These changes were associated with intense tubular injury, endothelial damage, reductions in antioxidant enzymes and an inflammatory process observed in the renal outer medulla of the animals from this group. These changes were attenuated by treatment with calcitriol, which reduced the inflammation and increased the expression of vascular regeneration markers and antioxidant enzymes.

Previous Exercise Effects in Cisplatin-Induced Renal Lesions in Rats.

BACKGROUND/AIMS: Physical training has beneficial effects on endothelial function and can influence the regeneration of the endothelial cell. We investigated the effect of physical training on cisplatin (CP)-induced acute kidney injury and assessed the impact of training on endothelial structure and function, and on the inflammatory processes in rats. METHODS: We injected male Wistar rats subjected to previous physical training in treadmill running (trained, TR) or not (sedentary, SED) with CP (5 mg/kg) (TR+CP and SED+CP groups, respectively). Five days after the injections, blood and urine samples were collected to evaluate renal function and kidneys were harvested for morphological, immunohistochemical, enzyme-linked immunosorbent assay, and analysis of nitric oxide (NO) levels. RESULTS: Rats treated with CP showed increased levels of plasma creatinine and sodium and potassium fractional excretion. These alterations were associated with increase in tubulointerstitial lesions and macrophage number, reduction of endothelial cells, and increased VEGF, vimentin, and α-smooth muscle actin expression in the outer renal medulla in the SED+CP group. We also found increased levels of renal IL-1ß and increased excretion of monocyte chemoattractant protein-1 and transforming growth factor-ß compared with controls. These changes were milder in trained rats, associated with increased levels of renal tissue NO, and increased expression of p-eNOS and stromal cell-derived factor-1α (a chemokine involved in kidney repair) in the kidneys of CP-injected trained rats. CONCLUSIONS: The protective effect of previous training in CP-treated rats was associated with reduced endothelial cell lesions and increased renal production of NO in trained rats.

Upregulation of Nrf2 and Decreased Redox Signaling Contribute to Renoprotective Effects of Chemerin Receptor Blockade in Diabetic Mice.

Chemerin, acting through its receptor ChemR23, is an adipokine associated with inflammatory response, glucose and lipid metabolism and vascular function. Although this adipokine has been associated with the development and progression of kidney disease, it is not clear whether the chemerin/ChemR23 system plays a role in renal function in the context of diabetes. Therefore, we sought to determine whether ChemR23 receptor blockade prevents the development and/or progression of diabetic nephropathy and questioned the role of oxidative stress and Nrf2 in this process. Renal redox state and function were assessed in non-diabetic lean db/m and diabetic obese db/db mice treated with vehicle or CCX832 (ChemR23 antagonist). Renal reactive oxygen species (ROS) production, which was increased in diabetic mice, was attenuated by CCX832. This was associated with an increase in Nox 4 expression. Augmented protein oxidation in db/db mice was not observed when mice were treated with CCX832. CCX832 also abrogated impaired Nrf2 nuclear activity and associated downregulation in antioxidants expression in kidneys from db/db mice. Our in vivo findings highlight the role of the redox signaling and Nrf2 system as renoprotective players during chemerin receptor blockade in diabetic mice. The chemerin/ChemR23 system may be an important target to limit renal dysfunction associated with obesity-related diabetes.

Membranous glomerulonephritis associated with splenic marginal zone lymphoma mimicking multiple myeloma.

Glomerulonephritis may complicate the course of a wide variety of malignant diseases. However, there are relatively few reports of membranous glomerulonephritis (MGN) in patients with non-Hodgkin lymphoma (NHL). We describe for the first time a case of MGN associated with splenic marginal zone lymphoma with extreme plasmacytic differentiation and bone marrow infiltration mimicking multiple myeloma. We also reviewed the literature and summarize the clinical-pathological findings and the mechanisms involved in NHL-induced MGN. Our current case highlights the importance of a quick and correct diagnosis of the underlying disease and the value of a thorough physical examination. Clinicians should be aware of the possibility of an underlying hematologic malignancy in such cases, particularly in elderly patients with renal biopsy that shows the presence of atypical histology.

What lies beneath: Fabry nephropathy in a female patient with severe cerebrovascular disease.

Fabry disease is an X-linked inborn error of metabolism, which is caused by the deficiency of α-galactosidase A, leading to progressive accumulation of neutral glycosphingolipids and a-galactosyl breakdown products in most body fluids and several tissues, resulting in the clinical manifestations. The onset of Fabry disease symptoms in females is not observed as early as in males. We report a novel presentation of Fabry disease in a female patient with medical history of relapsing strokes and brain magnetic resonance angiography showing signs of microangiopathy and multiple lacunar strokes that were first diagnosed as Moyamoya disease (a chronic progressive cerebrovascular disease). The patient subsequently displayed increased levels of serum creatinine and proteinuria. Diagnosis of Fabry disease was made by a renal biopsy and was confirmed by molecular studies showing a missense mutation: c1066C > T (het) [R356W]. The diagnosis was delayed by 21 years with respect to her first symptom (stroke), probably because her initial clinical presentation was neurological and diagnosed as Moyamoya disease. Other factors that contributed to the delay of the diagnosis were the lack of acute or chronic pain (neuropathic pain) and angiokeratomas. Some similarities in the pathogenic aspects of the patient's vascular lesions lead us to speculate that this patient has Fabry disease, with a phenotype that had not yet been described. It is necessary to be aware of this possibility to avoid misdiagnosis of Fabry disease as Moyamoya disease.

Effect of Calcitriol on the Renal Microvasculature Differentiation Disturbances Induced by AT1 Blockade During Nephrogenesis in Rats.

Alterations in the renal vasculature during fetal programming can cause disturbances in renal structure and function that persist into adulthood. Calcitriol can affect cellular differentiation and proliferation, and promote endothelial cell maintenance, each of which is a key event in nephrogenesis. Calcitriol is a negative endocrine regulator of the renin gene. Rats exposed to renin-angiotensin system (RAS) antagonists during lactation have been shown to develop renal disorders, which demonstrated that the RAS may play an important role in mammalian kidney development. We evaluated the effects of calcitriol administration on losartan [angiotensin II receptor antagonist (ANGII), AT1]-induced changes in renal differentiation in rats during lactation. Rats treated with losartan showed alterations in renal function and structure that persisted into adulthood. These disruptions included hydronephrosis, papillary atrophy, endothelial dysfunction, and aberrant endothelial structure. These changes were mitigated by treatment with calcitriol. The results of our study showed that animals exposed to AT1 blockade during lactation exhibited altered renal microvasculature differentiation in adulthood that was attenuated by treatment with calcitriol.

Effect of the absence of interleukin-12 on mesangial proliferative glomerulonephritis induced by habu snake venom.

BACKGROUND: Interleukin-12 (IL12) participates in the pathophysiology of various experimental types of progressive glomerulonephritis, but its role in acute mesangial glomerulonephritis (AMG) induced by habu snake venom (HSV) has not been determined. This study aims to evaluate the effect of the absence of IL12 on AMG induced by HSV. METHODS: AMG was induced in IL12 knockout (IL12-/-) and C57Bl/6 (IL12+/+) mice by a single i.v. administration of HSV. Vehicle was used in control animals. Mice were studied after 3, 7, and 14 days (D3, D7, and D14). RESULTS: After treatment with HSV, IL12+/+ and -/- mice developed focal glomerular lesions, but groups of both lineages showed no statistical difference concerning albuminuria, serum creatinine, histopathology, number of cells by glomerular tuft, and glomerular tuft area. Compared to IL12+/+ mice, IL12-/- mice showed lower scores of glomerular desmin expression on D7 [1.55 (1.32; 1.65) vs. 1.12 (1.07; 1.22); p < 0.01] and D14 [1.60 (1.55; 1.75) vs. 1.20 (1.15; 1.20); p < 0.001], respectively, and lower scores of glomerular alpha-SMA expression on D14 [0.30 (0.21; 0.38) vs. 0.16 (0.26; 0.36); p < 0.001], respectively. CONCLUSION: The absence of IL12 reduced the activity of mesangial cells, but did not modify the course of HSV-induced AMG in mice.

Parthenolide reduces cisplatin-induced renal damage.

Inflammatory events contribute to cisplatin-induced renal damage. Cisplatin promotes increased production of reactive oxygen species, which can activate nuclear factor-kappaB (NF-kappaB) that lead to increased expression of proinflammatory mediators which could intensify the cytotoxic effects of cisplatin. In this study, we evaluated the effect of parthenolide, a selective inhibitor of NF-kappaB, on renal damage caused by cisplatin use. A total of 94 male Wistar rats were divided into six groups: Group A (18 rats) were treated with saline; Group B (12 rats) received dimethylsulfoxide plus saline (the solvent for parthenolide); Group C (12 rats) received parthenolide (3mg/kg) plus saline; Group D (20 rats) received cisplatin (5mg/kg, i.p.); Group E (12 rats) received dimethylsulfoxide plus cisplatin (5mg/kg, i.p.); and Group F (21 rats) received parthenolide (3mg/kg) plus cisplatin (5mg/kg, i.p.). Dimethylsulfoxide or parthenolide were administered at 24h and 1h prior to cisplatin injection, and again at 24h and 48h after. At 2, 3 and 5 days after saline or cisplatin injection, blood and urine samples were collected for measurement of creatinine, sodium and potassium and the kidneys removed for histological, morphometric, electrophoretic mobility shift assay (EMSA), apoptosis and immunohistochemical studies. Cisplatin-treated rats presented higher plasma creatinine, as well as greater immunostaining for ED1 (macrophages/monocytes) and NF-kappaB in the renal cortices and outer medullae. The increase of NF-kappaB activation was confirmed by EMSA. Cisplatin-injected rats also presented higher urinary levels of lipid peroxidation and acute tubular necrosis. All of these alterations were reduced by treatment with parthenolide. This effect seems to be related, at least in part, to the restriction of renal inflammatory process observed in parthenolide+cisplatin treated rats.

Effects of resveratrol on glycerol-induced renal injury.

Glycerol-induced renal lesions can have many causes, including increased oxidative stress and inflammation. Resveratrol, a polyphenolic phytoalexin found in grapes and red wine, is an antioxidant agent with anti-inflammatory effects. In the present study, we investigated the possible protective effect of resveratrol on glycerol-induced nephrotoxicity. Male Wistar rats were injected intramuscularly with 8 ml/kg of either 50% glycerol (n=18), glycerol+resveratrol (n=22), 0.15 M saline (n=14), saline+carboxymethylcellulose (n=10) or saline+resveratrol (n=8). The rats were killed 3 days after the injections, at which time the kidneys were removed for histological and immunohistochemical studies and lipid peroxidation determination. Blood and urine samples were collected in order to quantify sodium and creatinine. The results of the histological and immunohistochemical studies were scored according to the extent of damage and immunostaining, respectively, in the cortical tubulointerstitium. Lipid peroxidation was estimated by measuring malondialdehyde in renal tissue samples collected from control rats and glycerol-injected rats. By postinjection day 3, glycerol-only treated rats presented increases in plasma creatinine levels, as well as in fractional excretion of sodium and potassium (P<0.001). These increases were less pronounced in glycerol+resveratrol-treated rats (P<0.05). Cortical expression of macrophages, lymphocytes, nuclear factor-kappa B, heme oxygenase-1 and nitrotyrosine was greater in glycerol-treated rats than in controls (P<0.001). In addition, the histological findings for glycerol-treated rats were characteristic of acute tubular necrosis. Resveratrol attenuated all of these alterations (P<0.001). We conclude that resveratrol ameliorates glycerol-induced renal injury by suppressing the inflammatory process and by inhibiting lipid peroxidation.

ATP-sensitive potassium channel blockage attenuates cisplatin-induced renal damage.

BACKGROUND: Cisplatin-induced renal damage was associated with an inflammatory process. ATP-sensitive potassium channels can be involved in neutrophil migration. This study evaluated the effects of glibenclamide, an ATP-sensitive potassium channel blocker, on cisplatin-induced renal damage. METHODS: A total of 48 Wistar rats received glibenclamide (20 mg/kg/day, s.c.) and 24 h later, these animals, and an additional group of 45 rats, were injected with cisplatin (5 mg/kg, i.p.). In addition, 38 control rats were injected with saline, i.p. Twenty-four hours and 5 days after saline or cisplatin injections blood and urine samples were collected to evaluate renal function and the kidneys were removed for analysis of neutrophil accumulation, tumor necrosis factor-alpha and interleukin-1beta and histological and immunohistochemical studies. RESULTS: Cisplatin injection induced neutrophil recruitment and increased tumor necrosis factor-alpha and interleukin-1beta contents in renal cortices and outer medullae tissues. Cisplatin-treated rats also presented reduction in the glomerular filtration rate, as well as greater immunostaining for ED1 (macrophages/monocytes) and acute tubular necrosis. All of these alterations were reduced by treatment with glibenclamide. These effects seem to be related, at least in part, to the restriction of neutrophil recruitment and inflammatory process observed in the kidneys from glibenclamide+cisplatin-treated rats.

Effects of previous physical training on adriamycin nephropathy and its relationship with endothelial lesions and angiogenesis in the renal cortex.

AIMS: Adriamycin (ADR)-induced nephropathy is one of the most experimental models used in progressive kidney disease. A single dose of this drug induces a progressive and irreversible proteinuria that progresses to focal segmental glomerulosclerosis and tubulointerstitial lesions. Regular physical activity has been considered as a therapeutic intervention in several diseases. This study evaluated the influence of previous physical training in renal damage induced by ADR and the role of endothelial lesions and angiogenesis in this process. MAIN METHODS: Male Wistar rats were subjected or not to treadmill running for 4weeks and then injected with ADR (2.5mg/kg, i.v.) or saline. Twenty-four-hour urine samples were collected for albuminuria measurement, and blood samples were collected to measure plasma creatinine 60days after the injections. The kidneys were removed for histological, immunohistochemical, Western blot and ELISA studies. KEY FINDINGS: ADR-treated rats presented increases in plasma creatinine levels, albuminuria, podocyte damage, and enlargement of the tubular interstitial relative area, as well as higher macrophage numbers in the renal cortex, interleukin (IL)-1ß levels in renal tissue and urinary monocyte chemoattractant protein (MCP)-1, which were associated with reduction in vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS) expressions and peritubular capillary (PTC) density in renal cortex. These alterations were less intense in the animals subjected to previous exercise training. SIGNIFICANCE: Physical training prior to ADR injection reduced the renal damage induced by this drug. This effect was related to angiogenesis and reduction in the endothelial lesions and inflammatory process in the renal cortex of these animals.

Inhibition of nuclear factor-kappa B activation reduces glycerol-induced renal injury.

BACKGROUND: Glycerol injection induces acute tubular necrosis that can progress to interstitial fibrosis. The oxidative stress seen in glycerol-treated animals can activate the nuclear factor kappa B (NF-kappa B) system. The aim of this study was to investigate the expression of NF-kappa B and mitogen-activated protein kinases (MAPKs) in the renal cortex and to determine its relationship with structural and functional renal changes in rats treated with glycerol or glycerol plus pyrrolidine dithiocarbamate (PDTC), a nonspecific NF-kappa B inhibitor with antioxidant properties. METHODS: Male Wistar rats were injected intramuscularly with 8 ml/kg of either 50% glycerol (n=22), glycerol+PDTC (n=25) or 0.15 M saline (n=10). The rats were killed, and the kidneys removed at 5 or 30 days after injection. mmunohistochemical results were scored according to the extent of staining. Interstitial lesions were evaluated through morphometry. Lipid peroxidation was estimated by measuring malondialdehyde in urine samples from control rats and glycerol-injected rats. RESULTS: By postinjection day 5, glycerol-only treated rats presented transitory increases in plasma creatinine levels, as well as in fractional excretion of sodium and potassium (p<0.001), which were attenuated in glycerol+PDTC treated rats (p<0.05). Cortical expression of macrophages and NF-kappa B was greater in glycerol-treated rats than in controls (p<0.001). Glycerol-induced histological nd immunohistochemical changes were attenuated by the addition of PDTC (p<0.001), which also reduced the glycerol-induced increase in urinary malondialdehyde (MDA) levels (p<0.05). CONCLUSIONS: We conclude that PDTC attenuates glycerol-induced renal injury by reducing NF-kappa B expression and decreasing lipid peroxidation in the renal cortex.

Comparative study of multiple dosage of quercetin against cisplatin-induced nephrotoxicity and oxidative stress in rat kidneys.

Quercetin, a typical bioflavonoid ubiquitously present in fruits and vegetables, is considered to be helpful for human health. Cisplatin (cDDP) is one of the most active cytotoxic agents in the treatment of a wide range of solid tumors. The aim of this study was to investigate the possible effect of quercetin, a bioflavonoid with antioxidant potential, on cisplatin-induced nephrotoxicity and lipid peroxidation in rats. Gavage administrations of water, propylene glycol and quercetin (50 mg/kg) were made 24 and 1 h before saline or cDDP (5 mg/kg) ip injections and were repeated daily for 2, 5 or 20 subsequent days. Rats were killed 2, 5 and 20 days after ip injections, and blood and urine samples were collected to determine plasma creatinine, urine volume and osmolality. The kidneys were removed to determine the levels of thiobarbituric acid-reactive substances (TBARS) and for histological studies. Cisplatin increased lipid peroxidation, urine volume and plasma creatinine levels and decreased urine osmolality. Treatment with quercetin attenuated these alterations. These results demonstrate the role of oxidative stress and suggest a protective effect of quercetin on cisplatin-induced nephrotoxicity in adult Wistar rats.

Gleason score and tumor laterality in radical prostatectomy and transrectal ultrasound-guided biopsy of the prostate: a comparative study.

We aimed to compare Gleason score and tumor laterality between transrectal ultrasound-guided biopsy of the prostate (TRUSBX) and radical prostatectomy (RP). Some factors that could cause a discrepancy in results between these two procedures were also evaluated. Among the 318 cases reviewed, 191 cases were selected for inclusion in this comparative study. We divided the patients into two groups using the Gleason score: an intermediate/high-grade group (≥7) and a low-grade group (<6). Exploratory analyses were conducted for comparisons between groups. We also performed comparisons between TRUSBX and RP for tumor laterality. TRUSBX overestimated 6% and underestimated 24% cases in comparison with RP for Gleason score, and overestimated 2.6% and underestimated 46% cases compared with RP for tumor laterality. Biopsy specimens were slightly smaller in TRUSBX cases with underestimated tumor laterality (P < 0.05), and no relationship between the biopsy specimen size and underestimated Gleason score in TRUSBX was found. Prostatic volume showed no statistical correlation with the likelihood of under or overestimation (P > 0.05). Thus, our study showed that TRUSBX has a high likelihood of underestimating both the Gleason score and tumor laterality in prostate cancer (PCa). The size of the fragment appears to be an important factor influencing the likelihood of laterality underestimation and Gleason score overestimation via TRUSBX. Due to the high likelihood of underestimation of the Gleason score and tumor laterality by 12-core prostate biopsy, we conclude that this type of biopsy should not be used alone to guide therapy in PCa.

Role of myofibroblasts, macrophages, transforming growth factor-beta endothelin, angiotensin-II, and fibronectin in the progression of tubulointerstitial nephritis induced by gentamicin.

BACKGROUND: Animal models of aminoglycoside nephrotoxicity can show residual areas of interstitial fibrosis in the renal cortex. This study investigated the expression of fibronectin, alpha-smooth muscle actin (alpha-SM-actin), macrophages, endothelin,transforming growth factor-beta (TGF-beta) and angiotensin II (AII) in the renal cortex of rats, 5 and 30 days after stopping treatment with gentamicin, and the relationships with the histological features and renal function of these animals. METHODS: Forty-five female Wistar rats were injected with gentamicin, 40 mg/kg, twice a day for 9 days, and 11 controls were injected with 0.15 M NaCl solution. The animals were killed 5 or 30 days after these injections and the kidneys removed for histological examination, enzyme immunoassay and immunohistochemical studies. The histological and immunohistochemical results were evaluated by scores reflecting the extent of lesion or staining. The percentage of tubulointerstitial lesions was determined by morphometry. RESULTS: Gentamicin-treated rats presented a transitory increase in plasma creatinine levels. The immunohistochemical studies showed increased fibronectin, alpha-SM-actin, ED-1, endothelin, TGF-beta and AII staining in the renal cortex from rats 5 and 30 days after gentamicin compared to control (p < 0.05). The animals killed on day 30 also presented fibrosis and increased TGF-beta content in the renal cortex (p < 0.001), despite the recovery of renal function. The proportion of damaged areas was 23.17% +/- 5.23 in the renal cortex of these animals. CONCLUSIONS: Macrophages, myofibroblasts, TGF-beta, endothelin and AII may have contributed to the development of renal fibrosis in these rats.

Inhibition of nuclear factor-kappaB activation attenuates tubulointerstitial nephritis induced by gentamicin.

BACKGROUND: Animals treated with gentamicin can show residual areas of interstitial fibrosis in the renal cortex. This study investigated the expression of nuclear factor-kappaB (NF-kappaB), mitogen-activated protein (MAP) kinases and macrophages in the renal cortex and structural and functional renal changes of rats treated with gentamicin or gentamicin + pyrrolidine dithiocarbamate (PDTC), an NF-kappaB inhibitor. METHODS: 38 female Wistar rats were injected with gentamicin, 40 mg/kg, twice a day for 9 days, 38 with gentamicin + PDTC, and 28 with 0.15 M NaCl solution. The animals were killed 5 and 30 days after these injections and the kidneys were removed for histological and immunohistochemical studies. The results of the immunohistochemical studies were scored according to the extent of staining. The fractional interstitial area was determined by morphometry. RESULTS: Gentamicin-treated rats presented a transitory increase in plasma creatinine levels. Increased ED-1, MAP kinases and NF-kappaB staining were also observed in the renal cortex from all gentamicin-treated rats compared to control (p < 0.05). The animals killed on day 30 also presented fibrosis in the renal cortex despite the recovery of renal function. Treatment with PDTC reduced the functional and structural changes induced by gentamicin. CONCLUSIONS: These data show that inhibition of NF-kappaB activation attenuates tubulointerstitial nephritis induced by gentamicin.

A novel case report of sickle cell disease-associated immunoglobulin A nephropathy: the diagnostic value of erythrocyte dysmorphism evaluation.

Sickle cell disease is a severe disease with a genetic pattern; it may cause anemia, vaso-occlusive phenomena, and multiorgan injury. It may damage any renal compartment, thereby causing tubular abnormalities, papillary necrosis, or glomerulopathies such as focal and segmental glomerulosclerosis and membranoproliferative pattern. The clinical consequences are hematuria and proteinuria. Hematuria associated with SCD is characteristically isomorphic (non-glomerular). This case report describes a novel case of a patient with sickle cell disease who presented with proteinuria and microscopic dysmorphic (glomerular) hematuria. A renal biopsy revealed immunoglobulin A nephropathy. Despite the fact that immunoglobulin A nephropathy is the most commonly diagnosed glomerulonephritis worldwide, an association between this entity and sickle cell disease has not yet been reported, probably because all cases of hematuria in patients with sickle cell disease have been regarded as secondary to sickle cell disease. Thus, new approaches are necessary to differentiate these conditions, such as evaluation of urinary erythrocyte dysmorphism, even more so because these two entities have different therapeutic options, morbidity, and mortality rates.

Brazilian embauba (Cecropia pachystachya) extract reduces renal lesions in 5/6 nephrectomized rats.

INTRODUCTION: Cecropia pachystachya (CP) is a plant rich in polyphenols which inhibits the angiotensin-converting enzyme (ACE) in vitro. Angiotensin II (AII) has an important role in the renal lesion provoked by 5/6 nephrectomy (NE). This study evaluated the CP extract effect on renal lesions provoked by 5/6 NE. MATERIALS AND METHODS: Male Wistar rats submitted to 5/6 NE were treated or not treated with CP extract and followed for 90 days. Systemic blood pressure (SBP), albuminuria, renal functional and structural parameters, ACE activity, urinary levels of monocyte chemoattrant protein-1 (MCP-1) and transforming growth factor ß (TGF-ß) were evaluated. RESULTS: Albuminuria and hypertension were less intense in the treated (NE+CP) group compared to the untreated (NE) group. CP extract treatment reduced the fall in glomerular filtration rate observed in NE rats. Glomerulosclerosis, tubulointerstitial lesions, increase of macrophages and AII positive cells in the renal cortex, as well as increases in renal ACE activity, urinary levels of MCP-1 and TGF-ß were attenuated in NE rats by CP treatment. CONCLUSIONS: The treatment with CP extract reduced the SBP and functional and structural renal changes in 5/6 NE rats. These effects were associated with decreased AII expression, ACE activity and inflammation in the renal cortex.

Renal Development and Blood Pressure in Offspring from Dams Submitted to High-Sodium Intake during Pregnancy and Lactation.

Exposure to an adverse environment in utero appears to programme physiology and metabolism permanently, with long-term consequences for health of the fetus or offspring. It was observed that the offspring from dams submitted to high-sodium intake during pregnancy present disturbances in renal development and in blood pressure. These alterations were associated with lower plasma levels of angiotensin II (AII) and changes in renal AII receptor I (AT(1)) and mitogen-activated protein kinase (MAPK) expressions during post natal kidney development. Clinical and experimental evidence show that the renin-angiotensin system (RAS) participates in renal development. Many effects of AII are mediated through MAPK pathways. Extracellular signal-regulated protein kinases (ERKs) play a pivotal role in cellular proliferation and differentiation. In conclusion, high-sodium intake during pregnancy and lactation can provoke disturbances in renal development in offspring leading to functional and structural alterations that persist in adult life. These changes can be related at least in part with the decrease in RAS activity considering that this system has an important role in renal development.