73 yr old patient with ARF Gil Chernin Nephrology Dept. Tel-Aviv Sourasky Medical Center Case presentation y.o female patient 73
Cause of admission: Acute renal failure with progressive symptomatic anemia Case presentation y.o female patient 73 Cause of admission: Acute renal failure with progressive symptomatic anemia
Medical Hx: hypertension & hyperlipidemia poor compliance- no medications Case presentation y.o female patient 73 Cause of admission: Acute renal failure with progressive symptomatic anemia
Medical Hx: hypertension & hyperlipidemia poor compliance- no medications cholelithiasis Case presentation )months ago 3(- 28/6/05 weakness, weight loss (3Kg in 4 months),
dyspepsia and few days of watery diarrhea Case presentation ) months ago 3(- 28/6/05 weakness, weight loss (3Kg in 4 months), dyspepsia and few days of watery diarrhea ,Lab:Hb-11.5 g/dL MCV=93, MCH=31
Iron status not taken Urea 31 mg/dL, Creatinine-0.9 mg/dL K=4.4 mmol/l , Na=142 mmol/l Case presentation ) months ago 3(- 28/6/05 weakness, weight loss (3Kg in 4 months),
dyspepsia and few days of watery diarrhea ,Lab:Hb-11.5 g/dL MCV=93, MCH=31 Iron status not taken Urea 31 mg/dL, Creatinine-0.9 mg/dL K=4.4 mmol/l , Na=142 mmol/l !same since 2001
Case presentation ) months ago 3(- 28/6/05 Lab: Ca=9.7 mg/dl Cholesterol=282 mg/dl TG=146 mg/dl Alk Phos=53 U/l ALT=16 U/l AST=23 U/l
TSH= 1.79 mU/l Normal urine sediment Case presentation 7/05 Colonoscopy without pathological findings Refused gastroscopy
Actually feeling better without further Rx Normal gynecological exam No OTC or natural products Case presentation months later : again 2 wk weakness, no pain 3
Case presentation months later : again 2 wk weakness, no pain 3 Hb-8.7 mg/dL , creatinine 2.3 mg/dL Ultrasound: Normal-sized kidneys Gallstones Hypertension: Norvasc & Normiten Admitted 1 week later - Hb-8.0 ; Ct 2.4
Case presentation :Physical examination oriented without apparent distress BP 176/69, HR 66, Temp 36.6 , RR 13, Sat 98% Eyes: mild hypertensive retinopathy; no
uveitis Heart: normal S1S2, no murmers or rub Lungs:normal ; Abdomen: normal Neurology:normal ; No signs of edema Rectal exam: normal Case presentation
Lab: hematology Hb 8.7 g/dl WBC 5.1 HCT 26.7% Neut 66% MCV 95 Lymph 25%
MCH 31 Mono 6.4% Plt 143 Eos 1.5% ESR-50/1hr PT/PTT normal Smear normal
Case presentation Lab: Chemistry GLU 88mg/dl Tot.Protein 65gr/l Urea 80 mg/dl Alb 45gr/l
Ct 2.4 mg/dl Glob 20gr/l Na 140 mmol/l CPK 140 U/l K 4.7 mmol/l
LDH 344 Phos 3.7 mg/dl GPT 22 U/l Ca 8.8 mg/dl Uric A. 5.5 mg/dl Alk.phos 64 u/l
Fe 81 mcg/dl Folic A. 6.5 ng/ml TIBC sat 32% Vit B12 380 pg/ml Ferritin 142
ng/ml ABGs -normal Case presentation Lab: urine SG 1.010 RBC neg
pH 5.0 Glu neg Leucocytes neg Prot neg Microscopy: 0-2/slide granular casts, 0-2 / HPF normal RBC and WBC Hr urine protein 110 mg 24
Nit neg Case presentation Lab: CXR: Normal-sized heart, without
pathological findings ECG: NSR Echo: mild concentric hypertrophy US: Normal renal structure, Rt 10.5cm Lt 10.8cm, no hydronephrosis Duplex Doppler- normal
Case presentation Lab: ANA,C3,C4,ANCA,ANTI GBM,APLA HBV,HCV,HIV , SPEP, UPEP, TSH all normal range
Case presentation Lab: ANA,C3,C4,ANCA,ANTI GBM,APLA HBV,HCV,HIV , SPEP, UPEP, TSH all normal range ,Bone marrow aspirate: reactive
possible MDS ?diagnosis ?diagnosis If you could add only one ? question to your anamnesis
Biopsy Biopsy Biopsy
Biopsy Biopsy Biopsy Diagnosis-biopsy
glomeruli, 8/40 sclerotic . Unremarkable 40 changes of the non-sclerotic glomeruli Numerous basophilic calcifications of tubules and adjacent interstitium, highlighted by von-Kossa stain and which do not display birefringence in . polarized light Tubular epithelial degenerative changes and
.atrophy, with areas of interstitial fibrosis IF: Negative Diagnosis-biopsy A picture consistent with acute nephrocalcinosis Diagnosis-biopsy
A picture consistent with acute nephrocalcinosis ?Why Diagnosis-biopsy A picture consistent with acute nephrocalcinosis ?Why The patient is normocalcemic without known
!predisposing factors Diagnosis-biopsy A picture consistent with acute nephrocalcinosis ?Why The patient is normocalcemic without known !predisposing factors
Let us go back to the anamnesis Case presentation 7/05 Colonoscopy without pathological findings Refused gastroscopy
Actually feeling better without further Rx Normal gynecological exam No OTC or natural products Case presentation 7/05 Colonoscopy without pathological findings
Refused gastroscopy Actually feeling better without further Rx Normal gynecological exam No OTC or natural products Case presentation 7/05
Colonoscopy without pathological findings Preparation: 2 bottles of Soffodex Followed the instructions well Case presentation 7/05 Colonoscopy without pathological findings
Preparation: 2 bottles of Soffodex Followed the instructions well Diagnosis Acute Phosphate Nephropathy Following Oral Phosphate Bowel Purgative
?What happens with phospho-soda Fleet phosphosoda = monobasic sodium phosphate and dibasic sodium phosphate mmol/ml of inorganic phosphate or 4.24 131.75 mg/ml of elemental phspohorous bottle of Soffodex (45ml)= 191.25 mmol or 1
mg of phosphorous 5929 ?What happens with phospho-soda bottles ~ 12 times the daily normal diet 2 After second bottle: phosphor may rise 3-5.5 mg/dl , calcium may decrease 0.3 mg/dl ; lower K Age is a factor
Gumurdulu et al, J Gastroenterol Hepatol 2004 Belooseski Y et al , Arch Intern Med 2003 Impaired peristalsis could enhance absorption: Paralitic ileus, bowel obstruction, Hirschsprungs disease
What is the pathogenesis? Role of nephrocalcinosis :Massive cellular release of phosphate Tumor Lysis Syndrome - evidence for calcium-phosphate deposition with exclusion of uric acid nephropaty Kanfer A , BMJ 1979
What is the pathogenesis? Role of nephrocalcinosis :Other hyperphosphatemic cases -Animal models No evidence: Zager RA et al, J Lab Clin Med 1982 Evidence for depositions : Ritkas-Hointinga J et al,
Nutr 1992 J What is the pathogenesis? Role of nephrocalcinosis :Other hyperphosphatemic cases
-Animal models No evidence: Zager RA et al, J Lab Clin Med 1982 Evidence for depositions : Ritkas-Hointinga J et al, J Nutr 1992
-Humans No evidence in PM: McConnell TH, JAMA 1971 :Evidence X-linked familial hypophosphatemic rickets U et al , J Pediatrics 1992
Alon Acute phosphate nephropathy post OSPS - cases without biopsy Ahmed et al: 77 yr old female, 1 bottle Phosphor=27.8 Ca=4.6 Ct=1.0->5.0 ; discharged 2.5
Am J Gasteroenterol 1996 ! Orias et al: 76 yr old male, Ct=1.1 , 5 bottles Phosphor = 15.8 Ca=7.1 Need dialysis Baseline creatinine after 1 months Am J Nephrol 1999
Pathology- nephrocalcinosis Desmeules S et al : NEJM Sep 4, 2003 letter -First biopsy proven case yr old female patient 71 weeks after colonoscopy- malaise 2 Creatinine 1.0 -> 4.5 mg/dl, normal US
after 10 months creatinine=1.7 mg/dl Pathology-nephrocalcinosis Human Pathol, June 2004 Pathology-nephrocalcinosis Markowitz et al JASN , November 2005
Pathology-nephrocalcinosis Markowitz et al JASN , November 2005 native kidney biopsies (2000-2004) 7394 Pathology-nephrocalcinosis Markowitz et al JASN , November 2005
native kidney biopsies (2000-2004) 7394 cases of nephrocalcinosis 31 Pathology-nephrocalcinosis Markowitz et al JASN , November 2005 native kidney biopsies (2000-2004) 7394 cases of nephrocalcinosis 31
with ARF, normocalcemic with recent colonoscopy preperation of OSPS or Visicol 21 Pathology-nephrocalcinosis Markowitz et al JASN , November 2005
native kidney biopsies (2000-2004) 7394 cases of nephrocalcinosis 31 with ARF, normocalcemic with recent 21 colonoscopy preperation of OSPS or Visicol ! Actually only 4/31 without colonoscopy
Pathology-nephrocalcinosis Markowitz et al JASN , November 2005 Mean age 64; 17/21(81%) females; 17/21 white Mean baseline creatinine (19/21, -4 mo)= 1.0 with mild renal failure (1.2-1.7) 4 hypertensive; 14 on ACE-I/ARBs 16 Diuretics, 3 NSAIDs 4
DM-2 4/21, CAD 3/21 Pathology-nephrocalcinosis Markowitz et al JASN , November 2005 Mean time to biopsy 3.8 months hyperphosphatemic, all normocalcemic 7/16 mean 24 hr urine protein 256 mg
Mean creatinine at biopsy 3.7 mg/dl (from 3.9 ) most with chronic irreversible interstitial fibrosis and tubular atrophy (like non resolving ATN) Pathology-nephrocalcinosis Markowitz et al JASN , November 2005 Mean follow-up 16.7 months
ESRD -- > ( 3 RRT ,1 successful transplantation) improved (mean creatinine 2.4 mg/dl) but only four < 2.0 mg/dl zero returned to baseline 4/21
16/21 Food for thoughts ?Avoid OSPS at all elderly (reduced GFR) hypertensive (ACE-I/ ARBs)
Food for thoughts ?Avoid OSPS at all elderly (reduced GFR) hypertensive (ACE-I/ ARBs) Inform the patient- reemphasize hydration
Food for thoughts ?Avoid OSPS at all elderly (reduced GFR) hypertensive (ACE-I/ ARBs) Inform the patient- reemphasize hydration
Epidemiology Food for thoughts ?Avoid OSPS at all elderly (reduced GFR) hypertensive (ACE-I/ ARBs)
Inform the patient- reemphasize hydration Epidemiology Routine renal functions before and/or after ?colonoscopy Follow-up 01/05/06 Feeling better, Creatinine 1.7 (MDRD~31)
Dont blame me said the Gastroenterologist ?What happens with phospho-soda Diet phosphate 800-1800 mg/d
Meat and dairy phosphates- absorbed well Vegetable phosphate- less absorbable of circulating phosphate is filtered at the 85% glomerulus; 15% in complex ( e.g. proteins)
Case presentation Lab: BGs pH 7.319 HCO3 24.9 mmol/l PCO2 45 mmHg ?What happens with phospho-soda
:Filtered phosphate is reabsorbed actively in proximal tubule ; PTH influence passively reabsorbed in distal nephron 80%
10-12% Hyperphosphatemia inhibits PTH secretion. Higher phosphorus diet will raise only slightly the plasma phosphate in normal renal function
