Evaluation of Anemia in Angiotensin Converting Enzyme (ACE) Knockout Mice.

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 693-693
Author(s):  
Justin M Cole ◽  
Pierre Corvol ◽  
Kenneth E Bernstein
Keyword(s):  
Renal Failure ◽  
Angiotensin Ii ◽  
Serum Creatinine ◽  
Cell Mass ◽  
Elevated Serum ◽  
Blue Dye ◽  
Wild Type ◽  
Inhibitory Peptide ◽  
Total Blood ◽  
Ace Activity

P2 Using targeted homologous recombination, we made two lines of mice that lack ACE. ACE.1 mice are null for all ACE activity while ACE.2 mice lack tissue ACE but retain 1/3 normal plasma ACE activity. Both strains have a marked decrease in blood pressure and are unable to produce a concentrated urine. ACE.1 mice have renal failure, as measured by a reduced creatinine clearance and an elevated serum creatinine, when compared to wild type mice; ACE.2 mice have no evidence of renal failure as indicated by a normal serum creatinine and creatine clearance. Surprisingly, both ACE.1 and ACE.2 mice are anemic with a reduction in hematocrit (38.5 +/- 1.3% and 38.3 +/- 0.8% respectively vs 48.4 +/- 0.9% for wild type) and serum hemoglobin (12.0 +/- 0.3 mg/dl and 11.7 +/- 0.2 mg/dl vs 14.7 +/- 0.3 mg/dl for wild type). In both strains, serum erythropoietin is elevated. Neither strain differs from wild type in regard to MCV, MCH, or MCHC, nor does either strain show chemical evidence of iron deficiency or hemolysis. Both ACE.1 and ACE.2 mice have equally low serum angiotensin II levels with a significant elevation of serum angiotensin I and the stem cell inhibitory peptide AcSDKP. Due to the presence of renal failure in ACE.1 mice, we have characterized in detail the anemia of ACE.2 mice. These animals demonstrate a significant reduction in total circulating red cell mass (24.2 +/- 1.1 μl/g vs 31.7 +/- 1.8 μl/g for wild type mice) without a change in total blood volume (57.8 +/- 1.2 μl/g vs 56.0 +/- 5.0 μl/g for wild type mice) as measured by the infusion of 51 Cr labeled erythrocytes. ACE.2 mice also have an increase in total plasma volume as determined by Evans Blue Dye infusion. The administration of angiotensin II to ACE.2 knockouts significantly increases their hematocrit and serum hemoglobin. Conclusion: The finding of significant anemia in ACE.2 mice, animals without renal failure, suggests a previously unappreciated role of the renin-angiotensin system in regulating erythropoiesis.

P1244MILD DIFFERENCES IN CARDIAC CALCIFICATION BETWEEN WILD TYPE AND SCLEROSTIN KNOCKOUT MICE WITH CKD

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Annelies De Maré ◽  
Patrick D'Haese ◽  
Anja Verhulst
Keyword(s):  
Renal Failure ◽  
Soft Tissue ◽  
Bone Formation ◽  
Serum Creatinine ◽  
Calcium Content ◽  
Serum Levels ◽  
Ectopic Calcification ◽  
Wild Type ◽  
Protective Function ◽  
Flame Atomic Absorption

Abstract Background and Aims Ectopic soft tissue calcifications, especially cardiovascular calcifications, are frequently observed in patients with chronic kidney disease (CKD) and are associated with increased morbidity and mortality. Sclerostin, a well-known inhibitor of bone formation, shows significantly increased serum levels in CKD patients. Since the process of ectopic calcification shares many similarities with physiological bone formation, we investigated a possible role for sclerostin in ectopic calcification development. Method CKD was induced in wild type (WT) (n=21) and sclerostin knockout (Sost ko) mice (n = 21), both on a C57Bl6/J background, by the alternate administration of a 0.30% and 0.15% adenine supplemented diet, containing 1% phosphate. A normal renal function control group receiving standard mouse chow (WT C57Bl6/J n = 8) was also included in the study. Serum creatinine and phosphate levels were measured at the start and end of the study to assess CKD development. At sacrifice, the calcium content of the kidneys, heart and aorta was determined by flame atomic absorption spectrometry. Results The adenine-supplemented diet led to a clear induction of CKD in both the Sost ko and wild type mice, as reflected by increased serum creatinine (0.38 ± 0.09 mg/dL in control mice vs 0.65 ± 0.18 mg/dL in adenine-exposed mice, p<0.0001) and phosphate levels (9.12 ± 1.16 mg/dL in control mice vs 19.03 ± 3.11 mg/dL in adenine-exposed mice, p<0.0001). The Sost ko and WT mice receiving the adenine diet, developed the same degree of renal failure, since there were no differences in serum levels of creatinine (p=0.0507) and phosphate (p=0.4890). Significantly higher amounts of calcium were measured in the kidney (0.05 ± 0.01 mg/g wet tissue vs 3.70 ± 2.00 mg/g wet tissue, p<0.0001) and the heart (0.03 ± 0.01 mg/g wet tissue vs 0.07 ± 0.04 mg/g wet tissue, p<0.0001) of adenine-exposed mice, compared to mice receiving the control diet. Furthermore, Sost ko mice had a significantly higher calcium content in the heart compared to the WT mice with renal failure (0.05 ± 0.03 mg/g wet tissue in WT mice vs 0.08 ± 0.05 mg/g wet tissue in Sost ko mice, p = 0.0029). No differences were observed in aortic calcium content between control mice and mice with renal failure. Conclusion In this study we managed to develop a mouse model of CKD-induced soft tissue calcification in the heart and kidneys of the animals, however no calcifications developed in the aorta. The higher calcium content that was observed in the heart of Sost ko mice compared to WT mice, might be an indication of a protective function of sclerostin during ectopic cardiac calcification

Treatment of Patients with Multiple Myeloma Complicated by Renal Failure with Bortezomib - Based Regimens.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2739-2739 ◽  
Author(s):  
Maria Roussou ◽  
Efstathios Kastritis ◽  
Athanasios Anagnostopoulos ◽  
Erasmia Psimenou ◽  
Irini Grapsa ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Renal Function ◽  
Serum Creatinine ◽  
Median Time ◽  
Objective Response ◽  
Elevated Serum ◽  
Management Problem ◽  
Newly Diagnosed ◽  
Kinetics Of

Abstract Introduction: Renal failure is a common feature of multiple myeloma and a major management problem. There is limited data regarding the reversibility of renal failure, the kinetics of serum creatinine and the safety of novel agents, such as bortezomib, when administered to newly diagnosed or relapsed/refractory patients with renal failure. The purpose of our analysis was to assess the frequency of renal failure improvement and kinetics of serum creatinine in patients who received bortezomib-based regimens. Patients and methods: We evaluated 20 consecutive patients with newly diagnosed (n=7) or relapsed/refractory (n=13) multiple myeloma and renal failure, defined as a serum creatinine ≥ 2mg/dl. Patients’ median age was 66 years (range 43–88 years). Median serum creatinine was 3.8 mg/dl (range 2–11.9 mg/dl) and median creatinine clearance was 15.3 ml/min (range 6.4–33.3). Other features included hemoglobin <10gr/dl in 12 patients, platelets <100 × 109/l in 3 patients and elevated serum LDH in 9 patients. All patients received bortezomib plus dexamethasone alone or in combination with other agents, such as thalidomide, doxorubicin or melphalan. Reversibility of renal failure was defined as a sustained decrease of serum creatinine to <1.5 mg/dl and renal response was defined as ≥50% decrease of serum creatinine from its peak value. Results: Reversal of renal failure was documented in 35% of all patients and the median time to reversal was 23 days. Moreover, 9 patients (45%) had 50% decrease in serum creatinine and the median time to decrease was 34 days. Some decrease of creatinine was documented in 88% of patients. Among four patients who were on renal dialysis, 2 became independent of this procedure after the second and the third cycle of treatment. The objective response rate was 61% and the median progression free survival for responders was 12 months. Toxicities were similar to those seen in myeloma patients without renal failure who were treated with bortezomib-based regimens. Grade 3–4 neutropenia and thrombocytopenia were seen in 28% and 22% of patients respectively. One patient died of infection and bortezomib had to be discontinued in 4 patients due to grade III neurotoxicity. Conclusions: When bortezomib-based regimens are administered to myeloma patients with renal impairment their toxicity and efficacy are similar to those observed in patients with normal renal function. Moreover, these regimens are associated with rapid improvement of renal function in most patients and with reversal of renal failure in one-third of them.

scholarly journals Renal Failure and Hepatitis Following Ingestion of Raw Grass Carp Gallbladder: A Case Report

2020 ◽  
Author(s):  
Lina Zhou ◽  
Shaoshao Dong ◽  
Shengze Zhang ◽  
Wen Huang
Keyword(s):  
Renal Failure ◽  
Serum Creatinine ◽  
Grass Carp ◽  
Elevated Serum ◽  
Food Poisoning ◽  
Organ Damage ◽  
The People ◽  
Folk Remedy ◽  
History Of

Abstract Background: Fish gallbladder has long been used as folk remedy in Asian countries.Multiple organ damage after fish gallbladder ingestion resulting in near mortality has been known to occur.Here,we describe a case of grass carp gallbladder poisoning and review the literature.Case Presentation: A previously healthy, 50-year-old woman was admitted to our hospital with a 2-day history of generalized abdominal pain and repeated vomiting following ingestion of 2 raw, grass carp gallbladders in an attempt to alleviate her cough. She developed anuria on day 4 with markedly elevated serum creatinine, urea, bilirubin, alanineaminotransferase, and aspartate aminotransferase.Based on thorough evaluation of her history and prompt biochemical investigations, we diagnosed her with acute renal failure and hepatitis secondary to fish gallbladder poisoning.Her renal biopsy revealed acute tubular necrosis.And she underwent six sessions of conventional hemodialysis due to renal failure. Supportive treatment, like gastric mucosal protectant and liver protectant were administered for targeted organ protection.The patient’s liver function gradually recovered and serum creatinine was 164 ummol/l at discharge on day 24. Over a period of 2-week follow-up, her renal function completely recovered. Conclusion: The purpose of this paper is to highlight the need for physicians to be mindful of the toxic complications of raw grass carp gallbladder ingestion and to promote its awareness among the people to help reduce this incidence of food poisoning.

Predicting renal outcome in IgA nephropathy.

1997 ◽  
Vol 8 (2) ◽  
pp. 199-207 ◽  
Author(s):  
M G Radford ◽  
J V Donadio ◽  
E J Bergstralh ◽  
J P Grande
Keyword(s):  
Renal Failure ◽  
Multivariate Analysis ◽  
Serum Creatinine ◽  
Iga Nephropathy ◽  
Adverse Outcome ◽  
Elevated Serum ◽  
Renal Outcome ◽  
Ki 67 ◽  
Component Scores ◽  
Mib 1

Immunoglobulin A (IgA) nephropathy, the most common form of glomerulonephritis worldwide, is characterized by a heterogeneous clinical course. In this study, multivariate analysis was performed to identify histopathologic and clinical features that most accurately predict adverse outcome from a dataset of 148 individuals with IgA nephropathy who underwent renal biopsy at our institution between 1973 and 1995. A semiquantitative scoring system was developed for assessment of six glomerular, eight interstitial, and six vascular histopathologic features of IgA nephropathy. Glomerular and interstitial proliferative activity was evaluated by immunostaining archival biopsy specimens with Mib-1, an antibody directed against the Ki-67 antigen. Kaplan-Meier survival analysis was performed, with renal failure being defined as onset of dialysis or transplantation. A number of clinicopathologic factors were univariately associated with adverse outcome, including elevated serum creatinine levels; the presence of hypertension; proteinuria; component and total histopathologic scores; and positive glomerular or interstitial Mib-1 scores. The total glomerular score, consisting of the arithmetic sum of each of the six component scores, was the strongest histopathologic predictor of adverse outcome. Total interstitial and vascular scores also provided more prognostic information than did individual component scores. By multivariate analysis, high total glomerular scores, increased serum creatinine levels at diagnosis, and younger age were significant (P < 0.01) independent predictors of renal failure. Our studies provide a rational basis for the inclusion of composite histopathologic scores in clinical intervention studies of patients with IgA nephropathy and other glomerular disorders.

scholarly journals The elevated serum urea : creatinine ratio in canine babesiosis in South Africa is not of renal origin

2006 ◽  
Vol 77 (4) ◽  
Author(s):  
M.P. De Scally ◽  
A.L. Leisewitz ◽  
R.G. Lobetti ◽  
P.N. Thompson
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Serum Creatinine ◽  
Cystatin C ◽  
Elevated Serum ◽  
Serum Urea ◽  
Canine Babesiosis ◽  
Serum Cystatin C ◽  
Serum Cystatin ◽  
Renal Origin

Pigmented serum, usually due to free haemoglobin and/or bilirubin, is a common finding in dogs with babesiosis, resulting in interference with all biochemical tests that rely on photochemistry. This is particularly true of urea and creatinine determinations, complicating the diagnosis of acute renal failure, which is a serious complication of babesiosis. A disproportionately raised serum urea concentration of unknown origin occurs in severely anaemic canine babesiosis patients and gives rise to an increased serum urea:creatinine ratio. The assay for cystatin-C, an excellent measure of glomerular filtration rate, is unaffected by free serum haemoglobin, and due to its different intrinsic origins, is free of influence by the metabolic derangements and organ pathology, other than renal disease, encountered in canine babesiosis. Serum cystatin-C was used to compare the concentrations of serum urea and serum creatinine in dogs with the severely anaemic form of canine babesiosis as well as a canine babesiosis-free reference group. Mean serum urea and mean serum urea:creatinine ratio were significantly elevated in the babesia-infected group relative to the reference population in this study. Mean serum creatinine and mean serum cystatin-C were within the reference ranges. Therefore an elevated urea:creatinine ratio in canine babesiosis in the presence of a normal serum creatinine concentration is considered to be caused by an elevated serum urea concentration and is most likely of non-renal origin. Serum creatinine was therefore as specific a measure of renal function as serum cystatin-C in canine babesiosis in this study. The sensitivity of serum creatinine as a measure of renal function was not established by this study. Serum urea, however, proved to be of little use compared to serum cystatin-C and serum creatinine. Serum urea should therefore not be used to diagnose renal failure in canine babesiosis.

scholarly journals A Healthy Active Duty Soldier with an Elevated Serum Creatinine

2021 ◽  
Author(s):  
Trevor W Tobin ◽  
John S Thurlow ◽  
Christina M Yuan
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Serum Creatinine ◽  
Renal Injury ◽  
Elevated Serum ◽  
Active Duty ◽  
Medical Problems ◽  
Sports Supplements ◽  
Elevated Serum Creatinine ◽  
Elevated Creatinine

ABSTRACT Creatine products and sports supplements are widely used by active duty soldiers. These products are associated with both acute renal failure and elevated serum creatinine levels without renal injury. We present a case involving an active duty, 26-year-old Caucasian soldier who was evaluated in our clinic for elevated creatinine levels. This patient had no active medical problems and was noted on repeat labs to have significantly elevated creatinine levels. Subsequent investigations led us to conclude these values were not associated with renal injury and were due to ingested supplements.

scholarly journals Waldenström’s Macroglobulinemia: Correlation Between Expanded Plasma Volume and Increased Serum Viscosity

Blood ◽  
1970 ◽  
Vol 35 (3) ◽  
pp. 394-408 ◽  
Author(s):  
MALCOM R. MACKENZIE ◽  
ELLEN BROWN ◽  
H. H. FUDENBERG ◽  
LUCY S. GOODENDAY
Keyword(s):  
Plasma Volume ◽  
Cell Mass ◽  
Elevated Serum ◽  
Signs And Symptoms ◽  
Red Cell ◽  
Aldosterone Secretion ◽  
Total Chromium ◽  
Total Blood ◽  
Volume Increase ◽  
Red Cell Mass

Abstract In 17 patients with Waldenström’s Macroglobulinemia, total chromium space, red cell mass, plasma volume and relative serum viscosities were determined; aldosterone excretion was determined in 12. Ten of the 15 patients who manifested elevated serum viscosity at some time during the course of study presented signs and symptoms of hyperviscosity syndrome. All patients had increased total blood volume. Fifteen had moderate decreases in red cell mass but all had elevations of plasma volume far in excess of that required to compensate for the lowered cell mass. The degree of the increase in plasma volume correlated (r = 0.74) with the degree of abnormality in relative serum viscosity. Aldosterone excretion in such patients was normal to low. It is concluded that the plasma volume increase is correlated with serum viscosity and is mediated by sodium retention mechanisms not involving modification of aldosterone secretion.

scholarly journals Protease-Activated Receptor 1 Mediates Thrombin-Dependent, Cell-Mediated Renal Inflammation in Crescentic Glomerulonephritis

2000 ◽  
Vol 191 (3) ◽  
pp. 455-462 ◽  
Author(s):  
Malcolm A. Cunningham ◽  
Eric Rondeau ◽  
Xin Chen ◽  
Shaun R. Coughlin ◽  
Stephen R. Holdsworth ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Renal Injury ◽  
Inflammatory Cell ◽  
Crescentic Glomerulonephritis ◽  
Elevated Serum ◽  
Control Treatment ◽  
Fibrin Deposition ◽  
Wild Type ◽  
Crescent Formation ◽  
Dependent Cell

Protease-activated receptor (PAR)-1 is a cellular receptor for thrombin that is activated after proteolytic cleavage. The contribution of PAR-1 to inflammatory cell–mediated renal injury was assessed in murine crescentic glomerulonephritis (GN). A pivotal role for thrombin in this model was demonstrated by the capacity of hirudin, a selective thrombin antagonist, to attenuate renal injury. Compared with control treatment, hirudin significantly reduced glomerular crescent formation, T cell and macrophage infiltration, fibrin deposition, and elevated serum creatinine, which are prominent features of GN. PAR-1–deficient (PAR-1−/−) mice, which have normal coagulation, also showed significant protection from crescentic GN compared with wild-type mice. The reductions in crescent formation, inflammatory cell infiltration, and serum creatinine were similar in PAR-1−/− and hirudin-treated mice, but hirudin afforded significantly greater protection from fibrin deposition. Treatment of wild-type mice with a selective PAR-1–activating peptide (TRAP) augmented histological and functional indices of GN, but TRAP treatment did not alter the severity of GN in PAR−/− mice. These results indicate that activation of PAR-1 by thrombin or TRAP amplifies crescentic GN. Thus, in addition to its procoagulant role, thrombin has proinflammatory, PAR-1–dependent effects that augment inflammatory renal injury.

scholarly journals Severe acute interstitial nephritis secondary to minocycline use in an adolescent girl

2020 ◽  
Vol 8 ◽  
pp. 2050313X2094306 ◽  
Author(s):  
Kamal Sharma ◽  
Nicholas Geagan ◽  
Supatida Tengsupakul
Keyword(s):  
Renal Failure ◽  
Serum Creatinine ◽  
Creatinine Level ◽  
Interstitial Nephritis ◽  
Elevated Serum ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
American Girl ◽  
Stage 1 ◽  
Echogenic Kidneys

Acute interstitial nephritis is an uncommon but classic complication of minocycline therapy for acne. A 14-year-old African American girl was started on oral minocycline for the treatment of acne 6 weeks before presentation. After 4 weeks on minocycline, she developed a generalized rash, anasarca, fever, myalgia, nausea, vomiting, sore throat, and generalized body weakness. The evaluation showed increased levels of serum creatinine, urea nitrogen, and serum alanine and aspartate aminotransferases. Renal ultrasonography showed bilateral enlarged, echogenic kidneys, and percutaneous renal biopsy showed features of acute allergic interstitial nephritis. Treatment included methylprednisolone and intravenous fluids and discontinuation of minocycline. The elevated serum creatinine level (12.9 mg/dL (reference, 0.40–0.70 mg/dL)) suggests marked renal impairment corresponding with Kidney Disease Improving Global Outcomes acute kidney injury classification stage 3. The kidney injury improved from stage 3 to stage 1 within 3 days, and early treatment with steroids might have prevented chronic renal failure. The creatinine level promptly decreased to normal, and liver enzyme results also improved. In summary, the diagnosis of acute interstitial nephritis should be considered in patients who present with renal failure associated with recent use of minocycline, and treatment with corticosteroids should be considered early during the hospitalization.

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