1 st JAMAICAN PAEDIATRIC NEPHROLOGY CONFERENCE

Transcription

1 in association with 1 st JAMAICAN PAEDIATRIC NEPHROLOGY CONFERENCE Jamaica Conference Centre Kingston Jamaica October 4 th 2014

2 Demys&fying Renal Tubular Acidosis Rulan S. Parekh Professor of Pediatrics and Medicine Hospital for Sick Children University of Toronto

3 None Disclosures

4 Outline Learning objecbves: Review acid handling in the kidney Pathophysiology of HCO3 reabsorpbon and H + excrebon Cases based discussion

5 Case 1 4 month old admiled with dehydrabon with probable rotavirus Work up includes electrolytes and HCO3 is 14 Normal saline is given in ER and then D5 0.2NS for maintenance HCO3 increases to 16 Nephrology is consulted for possible RTA

6 Ques&on What work up should be conducted? 1. Blood gas (venous or arterial) 2. Electrolytes (Na, K, Mg, Phos, Ca) 3. Renal funcbon and urinanalysis 4. Renal ultrasound 5. Detailed history and physical 6. Nothing

7 Ques&on What work up should be conducted? 1. Blood gas (venous or arterial)- depends 2. Serum or Urine Electrolytes (Na, K, Mg, Phos, Ca)- depends 3. Renal funcbon and urinanalysis- depends 4. Renal ultrasound- not yet 5. Detailed history and physical- absolutely 6. Nothing

8 Ini&al work- up for acidosis Acidosis Loss of buffer Add fixed acid Method to discriminate between the two possibilibes Serum Anion Gap

9 Ini&al work- up for acidosis Acidosis Loss of buffer Add fixed acid QuesBons Is there an anion gap acidosis? Is there systemic loss of HCO3 (ie diarrhea) If yes to either quesbon it is NOT an RTA

10 Case 1 4 month old admiled with dehydrabon with probable rotavirus Work- up includes electrolytes and HCO3 is 14; AG 10 Normal saline is given in ER and then D5 0.2NS is given for maintenance HCO3 increases to 16 and then drops to 13 Nephrology is consulted for possible RTA Ongoing loose stools SBll dehydrated Not an RTA iv fluids need to be consistent with ongoing stool losses

11 Ini&al work- up for acidosis Acidosis Loss of buffer Add fixed acid QuesBons: Is there a hyperchloremic nonanion gap metabolic acidosis: Normal renal funcbon? If yes to both: Possible RTA

12 Work- up for acidosis Acidosis Loss of buffer Add fixed acid (Chloride gain) GI Kidney Oral IV Diarrhea Fistula Ileal bladder Ca&on exchange resins CA inhibitors RTA Cl - HCI, NH 4 Cl - Parenteral nutri&on Dilu&on

13 Renal acid- base homeostasis Kidneys excrete meq/day of non carbonic acid generated daily Aim to: Keep all the bases Get rid of acid but not as free H + > 2 mmol/kg/day 2 main processes Proximal tubular absorpbon of HCO 3 - Distal urinary acidificabon ReabsorpBon of remaining HCO 3 - that escapes proximally ExcreBon of fixed acids through buffering & ammonia recycling and excrebon of NH 4 +

14 Na+/H+ exchanger isoform 3 (NHE3)-mediated bicarbonate reabsorption Di Sole F, and Girardi A C C Am J Physiol Cell Physiol 2011;301:C1290-C % 15%

15 Defini&on of RTA Hyperchloremic non anion gap metabolic acidosis QuesBon: Where in the kidney is the failure to reabsorb all filtered HCO3 with a net secrebon of H +?

16 Func&onal evalua&on of urinary acidifica&on Urine ph Urine anion gap Urine pco 2

17 Func&onal evalua&on of urinary acidifica&on Urine ph In humans, the minimum urine ph that can be achieved is 4.5 to 5.0 Measure in a fresh morning urine sample Urine should not be infected Urine anion gap Urine pco 2

18 Differences in urinary ph and plasma bicarbonate in proximal and distal RTA Urine ph become remains acidic(<5.5) mostly but becomes alkaline when bicarbonate losses are corrected. FEHCO3 increases(>15%)with administrabon of alkali for correcbon of acidosis

19 Func&onal evalua&on of urinary acidifica&on Urine ph Urine anion gap Urine pco 2

20 Urine AG = Urine (Na + K - Cl) Urinary excrebon of measured (Ca, Mg) and unmeasured anions (PO 4, SO 4, OAs) do not contribute significantly Major component of unmeasured cabons is NH 4 + Increase in NH 4 + excrebon accompanied by parallel increase in CI - secrebon Urine AG becomes more negabve as NH 4 + excrebon increases Urine AG has a negabve value in most pabents with a normal AG metabolic acidosis (normal in children: 0 to - 50) PaBents with renal failure, distal RTA or hypoaldosteronism are unable to excrete ammonium normally and the urine AG will be posibve

21 CAUTION!! BEWARE!! 2 semngs where urine anion gap (AG) is inaccurate Urine AG underesbmates NH 4 + U when excrebng large amounts of unmeasured anions such as: Ketoacids Penicillins NaCI deplebon (ie U Na < 25 meq/l) leads to low distal tubular delivery of Na

22 Func&onal evalua&on of urinary acidifica&on Urine ph Urine anion gap Urine Pco2 Measure of distal acid secrebon In prta, unabsorbed HCO 3 reacts with secreted H+ ions to form H2CO 3 that dissociate slowly to form CO 2 Urine- to- blood pco 2 is <20 in prta Urine- to- blood pco 2 is >20 in distal RTA reflecbng impaired ammonium secrebon

23 TYPES OF RTA Proximal RTA (type 2) Isolated bicarbonate defect Fanconi syndrome Distal RTA (type 1) GeneBc Secondary Hyperkalemic RTA (Type 4)

24 Case 2 2 year old presents to nephrology clinic for evaluabon of hypophosphatemia and growth delay EvaluaBon showed significant acidosis with HCO3 of 10, low phosphorus of 0.9,K is 2.9 and serum sodium of 129 Diagnosis is?

25 Schema&c model of HCO3 reabsorp&on in proximal convoluted tubule Rodríguez Soriano J JASN 2002;13:

26 Causes of Isolated Proximal RTA

27 Weiner I D, and Verlander J W Am J Physiol Renal Physiol 2011;300:F11-F23 Ammonia transport along the various renal epithelial segments

28 Case 2 2 year old presents to nephrology clinic for evaluabon of hypophosphatemia and growth delay EvaluaBon showed significant acidosis with HCO3 of 10, low phosphorus of 0.9, K is 2.9 and serum sodium of 129 Diagnosis is Fanconi s syndrome

29 Proximal RTA with Fanconi s- Congenital

30 Proximal RTA with Fanconi s- Acquired

31 Clinical presenta&on of proximal RTA Clinically- large losses of Bicarbonate Potassium Sodium PaBents with prta rarely develop nehrocalcinosis or nephrolithiasis In children, hypocalcemia and acidosis leads to growth retardabon, rickets, osteomalacia and abnormal vitamin D metabolism In adults, osteopenia can be seen

32 Case 3 10 year old girl is adopted from Korea and presents to the ER with abdominal pain Ultrasound shows non obstrucbng kidney stone Pain medicabons provided and sent home Comes to nephrology clinic and is evaluated for kidney stones AddiBonal history includes hearing loss and evidence of nephrocalcinosis

33 Schematic model of H+ secretion in cortical collecting tubule Rodríguez Soriano J JASN 2002;13:

34 Case 3 10 year old girl is adopted from Korea and presents to the ER with abdominal pain Ultrasound shows non obstrucbng kidney stone Pain medicabons provided and sent home Comes to nephrology clinic and is evaluated for kidney stones AddiBonal history includes hearing loss and evidence of nephrocalcinosis Labs show HCO3 is 15meq/L, K 3 meq/l and normal calcium and phosphorus Distal RTA

35 Gene&cs of RTA

36 Site of defect of distal RTA

37 E&ology of distal RTA

38 Clinical presenta&on of distal RTA Clinically present with hypercalciuria hypocitraturia nephrocalcinosis osteomalacia PaBents may nephrocalcinosis or nephrolithiasis Serum potassium is reduced in 50% of pabents increased kaliuresis to offset decreased H + and H- K- ATPase acbvity

39 Case 3 10 year old girl is adopted from Korea and presents to the ER with abdominal pain Ultrasound shows non obstrucbng kidney stone Pain medicabons provided and sent home Comes to nephrology clinic and is evaluated for kidney stones AddiBonal history includes hearing loss and evidence of nephrocalcinosis Labs show HCO3 is 15meq/L, K 3 meq/l and normal calcium and phosphorus Management with potassium citrate and free H 2 O No effect of hearing

40 Aldosterone and renal acidifica&on Favors H+ and K+ secrebon through enhanced sodium transport. Recruits more amiloride sensibve sodium channels in the luminal membrane of the collecbng tubule. Enhances H+- ATPase acbvity in corbcal and medullary collecbng tubules. Aldosterone also has an effect on NH4+ excrebon by increasing NH3 synthesis

41 Mechanism in distal RTA with hyperkalemia

42 Distal RTA with hyperkalemia Characterized by modest acidosis with hyperkalemia Occurs primarily due to decreased urinary ammonium excrebon Hypoaldosteronism is considered to be the most common ebology

43 E&ology of Distal RTA with hyperkalemia

44 Treatment- Proximal RTA A mixture of Na+ and K+ salts, preferably citrate, is preferable. 10 to 15 meq of alkali/kg may be required per day to stay ahead of urinary losses Thiazide diurebc may be beneficial if large doses of alkali are ineffecbve or not well tolerated SupplementaBon of all losses in Fanconi s syndrome

45 Treatment Distal RTA Bicarbonate wasbng can be negligible and can be treated with 1 to 2 meq/kg of sodium citrate (Bicitra) or bicarbonate. Potassium citrate, alone or with sodium citrate (Polycitra), is indicated for persistent hypokalemia or for calcium stone disease

46 Treatment Distal RTA with hyperkalemia Treatment and prognosis depends on the underlying cause Potassium- retaining drugs should always be withdrawn High- sodium, low- potassium diet plus a thiazide or loop diurebc if necessary. FludrocorBsone therapy may also be useful in hyporeninemic hypoaldosteronism, preferably in combinabon with a loop diurebc to reduce the risk of extracellular fluid volume expansion

47 Work- up for acidosis Acidosis Loss of buffer Add fixed acid (Chloride gain) GI Kidney Oral IV Diarrhea Fistula Ileal bladder Ca&on exchange resins CA inhibitors RTA Cl - HCI, NH 4 Cl - Parenteral nutri&on Dilu&on

48 Summary of evalua&on of RTA

49 Summary of evalua&on of RTA

50 Ques&ons