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Case Report: Acute Kidney Injury Due to Chronic Milk-Alkali Syndrome in a Patient With Colon Cancer.Frontiers in Medicine 2022Common causes of hypercalcemia include primary hyperparathyroidism and paraneoplastic syndrome of malignancy. Because of this, physicians can easily miss extrinsic...
BACKGROUND
Common causes of hypercalcemia include primary hyperparathyroidism and paraneoplastic syndrome of malignancy. Because of this, physicians can easily miss extrinsic causes of hypercalcemia such as milk-alkali syndrome in patients with cancer. We successfully treated a case of acute kidney injury due to severe hypercalcemia caused by milk-alkali syndrome due to long-term milk drinking in a patient with colon cancer.
CASE DESCRIPTION
A 62-year-old man was referred to nephrology for hypercalcemia and azotemia that was found during preoperative evaluation for colon cancer surgery. The patient had experienced several months of dizziness and anorexia. We started hemodialysis because hypercalcemia and azotemia were not improved despite large amounts of hydration and diuretics. We suspected paraneoplastic syndrome because of concomitant colon cancer and low intact parathyroid hormone (PTH). Renal microcalcifications were observed on ultrasonography. Metastatic calcifications of the lung and stomach were present, but no malignant metastasis appeared on bone scans. There was no evidence of metastatic malignant lesions on chest or abdominal enhanced computed tomography. PTH-related peptide was not detected. Thus, other causes of hypercalcemia beyond malignancy were considered. On history-taking, the patient reported consuming 1,000 to 1,200 mL of milk daily for the prior 3 months. Hypercalcemia was due to chronic milk-alkali syndrome. We advised withdrawal of milk and nutritional pills. Hemodialysis was stopped after 2 weeks since azotemia and hypercalcemia were resolving. Acute kidney injury was improved, and mild hypercalcemia remained when he underwent hemicolectomy after 1 month. Thereafter, serum calcium and creatinine remained normal at discharge and follow-up for 1 year in the outpatient clinic. However, lung calcifications still remained on bone scan after 1 year.
CONCLUSIONS
Chronic milk-alkali syndrome is a rare condition resulting from excessive calcium and alkali intake through various routes, like milk, nutritional supplements, and medicines for osteoporosis. Therefore, early management for hypercalcemia should include precise history taking including diet, previous diagnoses, and current medications.
PubMed: 35187010
DOI: 10.3389/fmed.2022.834107 -
JFMS Open Reports 2023A 3-year-old male neutered Sphynx cat was referred for history of chronically increased liver enzymes and lower urinary tract signs that were first reported when the cat...
CASE SUMMARY
A 3-year-old male neutered Sphynx cat was referred for history of chronically increased liver enzymes and lower urinary tract signs that were first reported when the cat was 5 months old. Urine metabolic profile revealed increased amino aciduria and glucosuria despite normoglycemia, suggesting Fanconi syndrome. Urine sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a banding pattern suggestive of primary tubular damage. Serial blood work showed non-regenerative normocytic normochromic anemia, persistently elevated liver enzymes, worsening azotemia and progressive hyperchloremic metabolic acidosis. Ultrasound revealed irregular kidneys and bilaterally hyperechoic cortices and medullae with a loss of normal corticomedullary distinction. Laparoscopic kidney biopsy revealed a moderate-to-severe chronic interstitial fibrosis with chronic lymphoplasmacytic inflammation, tubular degeneration and atrophy, mild glomerulosclerosis and mild large vascular amyloidosis. Tubular epithelial cell karyomegaly was multifocally evident throughout the kidney. The liver had moderate diffuse zone 1 hepatocellular atrophy, periportal fibrosis, biliary hyperplasia, mild perisinusoidal amyloidosis and hepatocyte karyomegaly in zones 2 and 3. The patient continued to decline and developed polyuria, polydipsia, lethargy and hyporexia irrespective of rigorous management, which failed to curtail the progressive anemia and azotemia. The patient was euthanized 8 months from the onset of clinical signs.
RELEVANCE AND NOVEL INFORMATION
Fanconi syndrome in cats is a rare condition, with most reports occurring secondary to chlorambucil treatment. This is the first known case of Fanconi syndrome occurring with concurrent hepatorenal epithelial karyomegaly in a young Sphynx cat.
PubMed: 37810577
DOI: 10.1177/20551169231190611 -
Journal of Veterinary Internal Medicine 2024Amyloid A (AA) amyloidosis is a protein misfolding disease arising from serum amyloid A (SAA). Systemic AA amyloidosis recently was shown to have a high prevalence in...
BACKGROUND
Amyloid A (AA) amyloidosis is a protein misfolding disease arising from serum amyloid A (SAA). Systemic AA amyloidosis recently was shown to have a high prevalence in shelter cats in Italy and was associated with azotemia and proteinuria.
OBJECTIVES
Investigate urine protein profiles and diagnostic biomarkers in cats with renal AA amyloidosis.
ANIMALS
Twenty-nine shelter cats.
METHODS
Case-control study. Cats with renal proteinuria that died or were euthanized between 2018 and 2021 with available necropsy kidney, liver and spleen samples, and with surplus urine collected within 30 days before death, were included. Histology was used to characterize renal damage and amyloid amount and distribution; immunohistochemistry was used to confirm AA amyloidosis. Urine protein-to-creatinine (UPC) and urine amyloid A-to-creatinine (UAAC) ratios were calculated, and sodium dodecyl sulfate-agarose gel electrophoresis (SDS-AGE) and liquid chromatography-mass spectrometry (LC-MS) of proteins were performed.
RESULTS
Twenty-nine cats were included. Nineteen had AA amyloidosis with renal involvement. Cats with AA amyloidosis had a higher UPC (median, 3.9; range, 0.6-12.7 vs 1.5; 0.6-3.1; P = .03) and UAAC ratios (median, 7.18 × 10 ; range, 23 × 10 -21.29 × 10 vs 1.26 × 10 ; 0.21 × 10 -6.33 × 10 ; P = .04) than unaffected cats. The SDS-AGE identified mixed-type proteinuria in 89.4% of cats with AA amyloidosis and in 55.6% without AA amyloidosis (P = .57). The LC-MS identified 63 potential biomarkers associated with AA amyloidosis (P < .05). Among these, urine apolipoprotein C-III was higher in cats with AA amyloidosis (median, 1.38 × 10 ; range, 1.85 × 10 -5.29 × 10 vs 1.76 × 10 ; 0.0 × 10 -1.38 × 10 ; P = .01). In the kidney, AA-amyloidosis was associated with glomerulosclerosis (P = .02) and interstitial fibrosis (P = .05).
CONCLUSIONS AND CLINICAL IMPORTANCE
Renal AA amyloidosis is associated with kidney lesions, increased proteinuria and increased urine excretion of SAA in shelter cats. Additional studies are needed to characterize the role of lipid transport proteins in the urine of affected cats.
Topics: Cats; Animals; Creatinine; Case-Control Studies; Kidney; Amyloidosis; Proteinuria; Serum Amyloid A Protein; Cat Diseases
PubMed: 37991136
DOI: 10.1111/jvim.16920 -
Journal of Hypertension Mar 2020Chromogranin A (CHGA) is an index granin protein critical for biogenesis and exocytotic release of catecholamine storage granules. It is elevated in plasma of patients...
BACKGROUND
Chromogranin A (CHGA) is an index granin protein critical for biogenesis and exocytotic release of catecholamine storage granules. It is elevated in plasma of patients with sympathetic over-activity and kidney dysfunction. Several CHGA polymorphisms are associated with hypertensive kidney disease. Previously, we unraveled the molecular mechanism by which CHGA expression is regulated in African Americans carrying a genetic variation associated with hypertensive chronic kidney disease (CKD).
METHOD
Experimental CKD mouse model were created by 5/6th nephrectomy (Npx) using wild-type and Chga-/- knockout mouse strains to delineate the role of CHGA in CKD.
RESULT
Wild-type-Npx mice expressing Chga developed exacerbated azotemia and fibrosis as compared with their knockout-Npx counterparts. Gene expression profiling revealed downregulation of mitochondrial respiratory complexes genes consistent with maladaptive mitochondria in wild-type-Npx mice, contrasted to knockout-Npx. In healthy individuals, an inverse relationship between circulating CHGA levels and glomerular function was observed. In vitro, mesangial cells treated with CHGA-triggered nitric oxide release by a signaling mechanism involving scavenger receptor SR-A. The CHGA-treated and untreated mesangial cells displayed differential expression of cytokine, chemokine, complement, acute phase inflammatory and apoptotic pathway genes. Thus, build-up of plasma CHGA because of kidney injury served as an insult to the mesangial cells resulting in expression of genes promoting inflammation, fibrosis, and progression of CKD.
CONCLUSION
These findings improve understanding of the role of elevated CHGA in the progression of CKD and reveal novel pathways that could be exploited for therapeutic strategies in hypertensive kidney disease.
Topics: Animals; Chromogranin A; Hypertension, Renal; Mice; Mice, Knockout; Nephritis
PubMed: 31714338
DOI: 10.1097/HJH.0000000000002295 -
Animals : An Open Access Journal From... Mar 2022Previous studies of azotaemia in canine babesiosis revealed pre-renal and renal azotaemia in infected dogs, and an association between an increased de Ritis quotient...
Previous studies of azotaemia in canine babesiosis revealed pre-renal and renal azotaemia in infected dogs, and an association between an increased de Ritis quotient (aspartate aminotransferase to alanine aminotransferase activity; AST/ALT ratio) and azotaemia in affected animals. Serum activities of AST and ALT, and AST/ALT ratio were compared between azotaemic and non-azotaemic dogs infected with , and between affected dogs with pre-renal and renal azotaemia. Statistical analyses revealed higher AST activity and an increased AST/ALT ratio in azotaemic dogs, and an increase of these two parameters in infected dogs with renal azotaemia in comparison to dogs with pre-renal azotaemia. Moreover, AST activity and AST/ALT ratio were correlated with renal indices such as renal failure index, sodium fractional excretion, and urinary creatinine to serum creatinine ratio. The study also revealed a lack of correlation between AST and ALT activities in azotaemic dogs, although a correlation was observed when including all dogs in this study (azotaemic and non-azotaemic dogs treated as one group). The results of this study indicate that increased serum AST activity in azotaemic dogs infected with may have a renal origin, and the AST/ALT ratio could be considered as a simple and convenient renal index that is useful in the recognition of renal azotaemia in canine babesiosis.
PubMed: 35268195
DOI: 10.3390/ani12050626 -
Schweizer Archiv Fur Tierheilkunde Jul 2022Little is known about the prognostic value of increased urine protein to creatinine ratios (UPC) comparing different underlying diseases in dogs. Therefore, between 2014...
Little is known about the prognostic value of increased urine protein to creatinine ratios (UPC) comparing different underlying diseases in dogs. Therefore, between 2014 and 2015, dogs with a UPC of 2,0 or higher measured were retrospectively analysed at least once. They were divided into groups of the most common underlying diseases, namely primary glomerulopathy, Cushing's disease, leishmaniasis and in a group of different diseases. Possible prognostic factors, like UPC at time of diagnosis, creatinine, urine specific gravity, albumin and haematocrit, were assessed. Eighty-nine dogs with severe proteinuria were included in the study. Median time of survival was 42 days. UPC and time of survival did not differ significantly between the groups. Among the dogs with primary glomerulopathy, identified significant risk factors for death included increased UPC (p=0,03), increased creatinine (p.
Topics: Animals; Creatinine; Dog Diseases; Dogs; Prognosis; Proteinuria; Retrospective Studies
PubMed: 35791822
DOI: 10.17236/sat00362 -
Nephrology, Dialysis, Transplantation :... Sep 2022Anemia and chronic kidney disease-mineral and bone disorder (CKD-MBD) are common and begin early in CKD. Limited studies have concurrently compared the effects of ferric...
BACKGROUND
Anemia and chronic kidney disease-mineral and bone disorder (CKD-MBD) are common and begin early in CKD. Limited studies have concurrently compared the effects of ferric citrate (FC) versus intravenous (IV) iron on CKD-MBD and iron homeostasis in moderate CKD.
METHODS
We tested the effects of 10 weeks of 2% FC versus IV iron sucrose in rats with moderate CKD (Cy/+ male rat) and untreated normal (NL) littermates. Outcomes included a comprehensive assessment of CKD-MBD, iron homeostasis and oxidative stress.
RESULTS
CKD rats had azotemia, elevated phosphorus, parathyroid hormone and fibroblast growth factor-23 (FGF23). Compared with untreated CKD rats, treatment with FC led to lower plasma phosphorus, intact FGF23 and a trend (P = 0.07) toward lower C-terminal FGF23. FC and IV iron equally reduced aorta and heart calcifications to levels similar to NL animals. Compared with NL animals, CKD animals had higher bone turnover, lower trabecular volume and no difference in mineralization; these were unaffected by either iron treatment. Rats treated with IV iron had cortical and bone mechanical properties similar to NL animals. FC increased the transferrin saturation rate compared with untreated CKD and NL rats. Neither iron treatment increased oxidative stress above that of untreated CKD.
CONCLUSIONS
Oral FC improved phosphorus homeostasis, some iron-related parameters and the production and cleavage of FGF23. The intermittent effect of low-dose IV iron sucrose on cardiovascular calcification and bone should be further explored in moderate-advanced CKD.
Topics: Animals; Biomarkers; Chronic Kidney Disease-Mineral and Bone Disorder; Ferric Compounds; Ferric Oxide, Saccharated; Fibroblast Growth Factors; Homeostasis; Iron; Male; Minerals; Parathyroid Hormone; Phosphorus; Rats; Renal Insufficiency, Chronic; Transferrins
PubMed: 35482713
DOI: 10.1093/ndt/gfac162 -
Indian Journal of Nephrology 2020Renal failure occurring in the setting of cirrhosis increases mortality by more than threefold. Serum creatinine, the conventional marker for renal dysfunction has...
BACKGROUND AND AIMS
Renal failure occurring in the setting of cirrhosis increases mortality by more than threefold. Serum creatinine, the conventional marker for renal dysfunction has inherent limitations in identifying and categorizing renal dysfunction in patients with chronic liver disease (CLD). Neutrophil gelatinase associated lipocalin (NGAL) is a novel biomarker which gets upregulated as early as 2-6 hours following the insult to renal tubules. In this study, we aim to check the utility of uNGAL to identify the different phenotypes of renal dysfunction in patients with CLD. We also intend to assess the utility of NGAL to predict 90-day transplant-free survival in patients with CLD.
METHODS
A total number of 120 adult patients, with cirrhosis of liver were recruited. Those with pre-existing renal parenchymal disease, receiving nephrotoxic medications, spontaneous bacterial peritonitis, septic shock, proteinuria, hematuria, urinary tract infection and anuria were excluded. Urine samples for NGAL was measured at admission and at 48 hours thereafter. Patients were followed up for 90 days post admission.
RESULTS
Among the study population, 16 patients (13.3%) had normal kidney function, 43 (35.8%) had prerenal azotemia and 54 (45%) had Hepatorenal Syndrome (HRS - AKI) and 7 (5.8%) had acute tubular necrosis (ATN). Urinary NGAL (uNGAL) levels were considerably lower in patients with normal kidney function and prerenal azotemia. An uNGAL level of 124 ng/ml on admission could distinguish severe forms of renal injury, with a sensitivity of 86% and specificity of 84%. The non survivors had higher uNGAL levels at admission [209.6 ng/ml (118.7-376.8) vs. 123 (33.6-344.3); = 0.013].The receiver operated curves for uNGAL and serum creatinine at admission did not show any significant difference for predicting 90 day mortality (AUC for uNGAL: 0.632 vs 0.580 for serum creatinine; difference in AUC 0.053, value 0.17).
CONCLUSION
uNGAL levels are elevated in patients with HRS-AKI and ATN. A higher uNGAL level at admission was suggestive of severe renal dysfunction. An elevated uNGAL on admission is associated with inferior survival. However, uNGAL is not superior to serum creatinine in predicting 90-day mortality.
PubMed: 33840958
DOI: 10.4103/ijn.IJN_254_19 -
Kidney360 Apr 2022Fractional excretion of urinary sodium (FENa) is a widely utilized clinical test to evaluate acute kidney injury (AKI). A low FENa (<1%) is deemed consistent with... (Observational Study)
Observational Study
BACKGROUND
Fractional excretion of urinary sodium (FENa) is a widely utilized clinical test to evaluate acute kidney injury (AKI). A low FENa (<1%) is deemed consistent with prerenal azotemia and inconsistent with acute tubular injury (ATI). Muddy brown granular casts (MBGC) on microscopic examination of urinary sediment (MicrExUrSed) are highly suggestive of ATI. We hypothesized that there is poor concordance between the presence of MBGC and FENa in ATI.
METHODS
We conducted a prospective observational study in patients with AKI seen during inpatient consultation. We extracted patients who underwent assessment of percentage of low power fields (LPFs) with MBGC by MicrExUrSed and concomitant measurement of FENa. Diagnostic concordance between MBGC and FENa and their individual prognostic value were examined.
RESULTS
Our cohort included 270 patients, 111 (41%) of whom were women. Median age was 61 years (range 27-92 years), and median serum creatinine was 3.7 mg/dl ( range1.2-22.0 mg/dl). MBGC were found in 49% (133/270). FENa <1% (inconsistent with ATI) was found in 50/133 (38%), 38/115 (33%), and 16/45 (36%) of those with >0%, ≥10%, and ≥50% LPFs with MBGC, respectively. Concordance between FENa and MBGC for ATI diagnosis was deemed fair (estimated -coefficient=0.2), and poor (=-0.11) within a subgroup of patients with preexisting chronic kidney disease (=139). In patients with biopsy-proven ATI (=49), MBGC had 100% specificity and 100% positive predictive value for ATI. MBGC were associated with greater risk for ≥50% increase in creatinine from baseline at discharge (acute kidney disease [AKD]).
CONCLUSIONS
About two of five patients with MBGC identified by MicrExUrSed presented with FENa <1%. Presence of MBGC was consistent with ATI, as verified by biopsy, and were predictive of AKD. These data suggest that the sole reliance in low FENa to exclude ATI should be abandoned, and MicrExUrSed should be pursued for AKI diagnosis.
Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Creatinine; Female; Humans; Kidney Function Tests; Male; Middle Aged; Sodium; Urinalysis
PubMed: 35721603
DOI: 10.34067/KID.0005692021 -
Open Veterinary Journal 2022No specific study on concurrent nephropathy has been conducted in dogs with chronic enteropathy (CE), except for soft-coated Wheaten Terriers. Moreover, limited...
BACKGROUND
No specific study on concurrent nephropathy has been conducted in dogs with chronic enteropathy (CE), except for soft-coated Wheaten Terriers. Moreover, limited information exists regarding the urinary profile in dogs with CE.
AIM
To describe, compare, and discuss the alterations in selected serum biochemical and urinary parameters in dogs with CE.
METHODS
Multicentric retrospective study on dogs with CE diagnosed after exclusion of extra-gastrointestinal diseases. In addition, dogs with azotemia and lower urinary tract diseases were excluded. Information on canine chronic enteropathy clinical activity index (CCECAI) score, muscular condition score (MCS), presence of glycosuria, proteinuria [urine protein-to-creatinine (UPC) ratio > 0.5], and/or cylindruria (>1-2 casts/hpf) at diagnosis were gleaned from the medical records. Dogs were retrospectively classified as food-responsive enteropathy, immunosuppressant-responsive enteropathy, or nonresponsive enteropathy based on the presence of gastrointestinal histological inflammation and the treatment response. In addition, based on the serum albumin concentration (ALB), dogs were classified as having protein-losing enteropathy (PLE).
RESULTS
Ninety CE dogs were included. Fifty-two dogs had mild-to-severely decreased MCS and 38 dogs showed altered urinary parameters. No significant associations were found between CCECAI and altered urinary parameters. No significant association was found between PLE dogs and altered urinary parameters. PLE dogs showed higher prevalence of proteinuria than non-PLE dogs ( = 0.03; OR = 2.8; 95% CI = 1-6.8).
CONCLUSION
Despite the presence of altered urinary profile in dogs with CE, further studies are needed to explore a possible link between gastrointestinal and renal inflammation.
Topics: Animals; Creatinine; Dog Diseases; Dogs; Immunosuppressive Agents; Inflammation; Inflammatory Bowel Diseases; Kidney Diseases; Protein-Losing Enteropathies; Proteinuria; Retrospective Studies; Serum Albumin
PubMed: 36118717
DOI: 10.5455/OVJ.2022.v12.i4.21