Presentation on theme: "Back to Basics Nephrology 2016"— Presentation transcript:
1 Back to Basics Nephrology 2016 Answers to the questions that we will cover during the session are at the end of this file. If you plan to attend the session, please wait till after to look at the answers.The link to the quiz questions will be active at the time of the session(More information for many slides can be found in the notes section of this PPT)
2 Back to Basics Nephrology 2016 This session is a brief review of the top renal issues that are likely to be tested on examsSome extra slides are included at the end of this PPT file. They are not thought to be required study material.
7 Urine values compatible with pre-renal failure: Click here with PowerPoint in slide show modeQuiz Question 1Urine values compatible with pre-renal failure:Osm < 300 mosm/LRBC castsNa+ < 20 mmol/LFex Na+ > 2%
8 ARFPre renal and ATN most common causes (quoted at 70% of cases of ARF)DDx:Pre RenalIntra RenalPost RenalThe term AKI, (Acute Kidney Injury), is being used in clinical research settings in place of ARF, but not on the MCCI would suggest NOT even thinking of memorizing the AKI criteria, but if you are really interested in them they are on the last slide of this PPT file.
9 Urine: Pre-Renal vs. Renal Assessment of Function U Na U Osm Fe NaPre-RenalATN< 20> 500< 1%> 40< 350> 2%U/P NaU/P CrThese values have been validated since the 1970sThe UNa, Uosm require that the patient be oliguricThe FeNa is much more predictive if the patient is oliguricFe Na =X 100Pigmented granular casts found in up to 70% of cases of ATN
10 Urine: Pre-Renal vs. Renal Assessment of Function Fe UreaPre-RenalATN< 35U/P UrU/P CrFe Urea =X 100> 55Personally, my take on what is published is that the FeUrea is not predictive for prerenal ARFFeUrea might be useful to Dx pre renal ARF in those who received diuretics…but not all studies support its use.
11 ARFInvestigations:Pre Renal: Urine tests as noted and responds to volumeIntra-Renal: look for GN, interstitial nephritis as well as ATNPost Renal: Imaging showing bilateral hydronephrosis is highly specific for obstruction causing ARFAlthough decreased intravascular volume can result in both pre renal ARF and in ATN the way to look at it is as follows:Pre renal ARF means no damage has been done to the nephrons, but the kidneys are not receiving the amount of plasma they need to be able to eliminate the amount of solute produced per day. Once the kidneys are supplied with this volume, they will be able to do their normal job.Ischemic ATN means that renal blood flow has been so low that ischemic damage has occurred to nephrons and even if renal blood flow is restored to normal, the kidneys will not resume normal function, typically for one to 3 weeks.
12 Dialysis: Who Needs It? If cannot control these by other means: HyperkalemiaPulmonary edemaAcidosisUremia(GFR < 8-12% for CRF depending on symptoms)NB in practice almost always, volume or hyperkalemia are the usual reasons to start dialysis in ARFIn ARF, dialysis has usually been started for volume or K before any uremic indications happen
13 Dialysis: Who Needs It?Hemodialysis is also used for intoxications with:ASALiAlcohols: i.e. methanol, ethylene glycolSometimes theophylline
15 K/DOQI Classification of Chronic Kidney Disease Stage GFR (≥3mo) Description(ml/min/1.73m2) Damage with normal GFRMild GFRModerate GFRSeverely GFR< Kidney FailureThis definition of CKD is now used by most nephrologists.Clinically, creatinine based estimates of GFR are not accurate above 60 ml/min/1.73m2 so we can only talk about stages 3,4 and 5, (and the formulae are not very good for GFR below 15).Approximately 500,000 Canadians have stage 3 CKD; most of these will not need renal replacement therapy
16 In this K/DOQI staging, “kidney damage” means: Persistent proteinuriaPersistent glomerular hematuriaStructural abnormality:such as PCKD, reflux nephropathyThe presence of proteinuria is a very important marker that predicts future decrease in GFR and cardiovascular mortality
17 CHRONIC KIDNEY DISEASE Diagnosis:Acute vs. chronic:Small kidneys on U/S or unenhanced imaging mean CKDDiabetic CKD may still have normal sized kidneysVery high PTH without hypercalcemia suggestive of secondary, (CKD) cause of increased PTHSome other causes of CKD and normal sized kidneys are myeloma, amyloid, and polycystic kidney disease
18 CHRONIC KIDNEY DISEASE Common causes of CKD:Diabetic nephropathyVascular diseaseGNPKDGN, (glomerulonephritis) here means glomerular disease due to primary, (idiopathic), causes other than secondary disease such as diabetic nephropathy.
19 CHRONIC KIDNEY DISEASE Causes of CKD:Best to divide as proteinuric or non-proteinuric CKDProteinuric is much more likely to have deterioration in GFR and higher cardiovascular morbidity and mortality
20 CHRONIC KIDNEY DISEASE TreatmentRule out acute changes:Pre RenalIntra RenalPost RenalRule out acute on chronic decrease in GFR using the ARF breakdown of causes.Especially remember: ACEI, ARBs, diuretics and NSAIDs with hypovolemia can cause acute decrease in GFR
21 CHRONIC KIDNEY DISEASE TreatmentDelay progression:Treat underlying disease i.e. good glucose control for DMBP control to 140/90, (the current target); 130/80 for diabeticsACEI or ARB has extra benefit for proteinuric CKDLower protein diet…maybeBP target guidelines are constantly changing. These are from 2014 Canadian Hypertension Education Program.
22 CHRONIC KIDNEY DISEASE Treatment of the consequences of decreased GFR:PO4:decrease dietary intakePO4 binders such as CaCO3Hypocalcemia:CaCO3, 1,25 OH D3Hyperphosphatemia and hypocalcemia typically does not occur until GFR falls below 30 ml/minTypical dietary sources of PO4 are dairy, meat, colasWith diet alone, it is difficult to keep PO4 normal as GFR declines toward the need for renal replacement and that is why CaCO3, (and other non calcium substances such as sevalemer), is used to bind PO4 in the GI tract and prevent it from being absorbed.NB: there is some concern that the use of CaCO3 may result in calcific blood vessel changes.Active 1,25 OH D3 is 1 hydroxylated in the kidney, 25 hydroxylated in the liver
23 CHRONIC KIDNEY DISEASE Treatment of the consequences of decreased GFR:Anemia:Erythropoetin current target HbAnemia in CKD does not usually occur till GFR is less than 30 ml/minStudies have shown increased mortality with targeting Hb closer to normal values and opinion re: target Hb varies
24 CHRONIC KIDNEY DISEASE Uremic Complications:Major:PericarditisEncephalopathyPlatelet dysfunctionUremic complications that are not life threatening include: nausea, vomiting, anorexia, prutitis
26 ASSESSMENT OF GFR:Creatinine concentration alone is not the best way to assess GFR
27 ASSESSMENT OF GFR: UCr x V PCr Creatinine clearance formula:24 hour urine creatinine clearance is not commonly done in 2015Need a Steady State for these to be valid
28 ASSESSMENT OF GFR: Cockroft-Gault estimated Creatinine clearance: (140-age) x Kg x x .85 for womenCreatNeed a Steady State for these to be valid
29 MDRD eGFR Need a Steady State for these to be valid GFR, in mL/min per 1.73 m2 = (170 x (PCr [mg/dL])exp[-0.999]) x (Age exp[-0.176]) x((Surea [mg/dL])exp[-0.170]) x ((Albumin [g/dL])exp[+0.318])where SUrea is the serum urea nitrogen concentration; and exp isthe exponential. The value obtained must be multiplied by ifthe patient is female or by if the patient is black.Simplified:GFR, in mL/min per 1.73 m2 =186.3 x ((serum creatinine) exp[-1.154]) x (Age exp[-0.203])x (0.742 if female) x (1.21 if African American)There are apps and online sites that do this calculationNeed a Steady State for these to be valid
30 Limitations of GFR estimates: Not reliable for: extremes of weight or different body composition such as post amputation, paraplegiaacute changes in GFRuse in pregnancyeGFR greater than 60ml/min/1.73m2As previously noted, creatinine based estimates of GFR are not accurate when calculation gives a value greater than 60ml/min in which case GFR is assumed to be normal unless there are strong risk factors for renal disease present.A nuclear GFR would be needed to measure GFR more accurately in the 60 to 90 ml/min range, for example, prior to nephrectomy in kidney donation. Even nuclear GFR may not be perfect.
31 Electrolyte and Acid-Base Disorders Sodium disordersHyperkalemiaHypomagnesemia and hypophosphatemiaAcid-Base disorders
33 HyponatremiaPseudo:If total osmolality is high: hyperglycemia/ mannitolIf total osmolality is normal, could be due to very high serum lipoprotein or proteinThe normal osmolality hyponatremia will happen only if Na is measured by the lab in a certain way, for example a flame photometer
34 Hyponatremia Volume status: Hypovolemic: high ADH despite low plasma osmolalityHigh total volume: CHF/ cirrhosis have decreased effective circulating volume and high ADH despite low plasma osmolalitySince we cannot get lab measurement of ADH, we use urine osmolality as a proxy.High urine osmolality tells us there is ADH present
35 Hyponatremia Volume status: If volume status appears normal: If urine osmolality is low: normal response to too much water intake…”psychogenic polydipsia”If urine osmolality is high: inappropriate ADHIf you see a hypo osmotic patient with a very low urine Osm of 50 mOsm/L, that patient has lowered their urine Osm appropriately in response to the hypo osmotic plasma and a high water intake is the likely problemNormally, people can drink 10 to 15 L of water per day without causing hypo Osmotic plasma, but I would not recommend anyone try this
37 Hyponatremia Treatment: Rate of correction of Na: Not more than 8-10 mmol in first 24 h and not more than 18 mmol over first 48 h of treatmentOr Central Pontine Myelinosis may occurThere is some reason, based on animal models, to think that if the Na has corrected too quickly, attempts to lower it back down with D5W and or ADH would have some benefit.Some of those at most risk for CPM are those with hypokalemia, alcoholism and females
39 Hypernatremia Usually decreased total body water: GI losses such as non secretory diarrheaRenal losses such as osmotic diuresis or lack of ADH secretion or lack of tubular effect of ADHLack of access to or ability to drink waterRarely from massive Na ingestion po or IV hypertonic salineNon secretory diarrhea: viral, bacterial, lactulose
40 HypernatremiaNo matter where the water loss occurs, thirst normally prevents hypernatremiaNeed a combination of lack of thirst and loss of water or hypotonic fluid to result in hypernatremia
41 Hypernatremia Management: Administration of hypotonic fluid and treating the underlying conditionCalculation of free water deficit gives an idea of how much water is needed, but need to check serum Na frequently to see if remain on target.Free water deficit (in litres) = Total body water x [(current serum Na/140) -1]
42 Hypernatremia Management: For chronic hypernatremia, (present for longer than 48 hours), do not correct more than 10 mmol/L per 24 hours, (this pertains most to pediatric patients, to prevent cerebral edema)For acute hypernatremia lower Na to close to normal within 24 hoursCalculation of free water deficit gives an idea of how much water is needed, but need to check serum Na frequently to see if remain on target.Free water deficit (in litres) = Total body water x [(current serum Na/140) -1]
44 Hyperkalemia Is it Real or Not: Hemolysis of sample Very high WBC, PLT Prolonged tourniquet timeECG changes such as peaked T waves, then flattened P waves and prolonged QRS may be seen with true hyperkalemia but are not always present with true hyperkalemia.
45 Hyperkalemia Shift of K from cells: Insulin lack High plasma osmolalityAcidosisBeta blockers in massive doses
46 Hyperkalemia Increased total body K: Decreased GFR plus: High diet KKCl supplementsACEI/ARBK sparing diureticsDecreased Tubular K secretion
47 TTKG?No longer usedSecond last slide of this PPT has information for those who still want to read about it.“Trans tubular potassium gradient”This formula relates to the basic physiology of K secretion from principal cells.In the past was interesting to use it clinically but it is no longer regarded as being helpful.
48 Hyperkalemia Treatment IV Ca Temporarily shift K into cells: Remove K Insulin and glucoseBeta 2 agonists (not as reliable as insulin)HCO3 if acidosis presentRemove KFor modest hyperkalemia, many use kayexalate po given with a non absorbable sugar such as lactulose or sorbitol or just water. Others argue that there is little evidence that it works.If kayexalate is given as an enema, do not use lactulose or sorbitol as these can damage colonic mucosa.
50 Magnesium Hypomagnesemia: GI loss/lack of dietary Mg Renal loss: DiureticsToxins esp cisplatin
51 Is hypoMg due to renal loss? Fractional excretion of Mg:FEMg= UMg/(0.7xPMg) X 100UCr/PCrShould be below 2% if Mg loss is extrarenal
52 Consequences of Hypomagnesemia Severe:Tetany, ventricular arrhythmiasAlso due to co-existent hypocalcemiaHypocalcemiaHypokalemiaTRIVIA: Hypomagnesemia causes hypocalcemia mostly by causing hypo responsiveness to PTH
53 Hypophosphatemia Shift: Refeeding with insulin release Hungry bones post parathyroidectomyResp alkalosis
54 Hypophosphatemia Decreased total body PO4 Renal loss GI loss Decreased intake, (rare)Vitamin D deficiencyRenal lossDiuretics, primary hyperparathyroidismFanconi Syndrome?Very rare renal tubular loss of:PO4, amino acids, glucose, HCO3-Fanconi syndrome appears more often on exams than in real life.In children usual cause is rare autosomal recessive disorder: cystinosisIn adults rarely caused by myeloma
56 Quiz Question 2 Most likely cause of Na 140 Cl 110 HCO3 10 : RTA serum albumin 20resp alkalosisketoacidosis
57 Acid-Base Approach to: Resp or metabolic Compensated or not If metabolic: anion gap or notAnion gap = Na - (Cl + HCO3)Remember that full compensation does not result in normal pH except in chronic respiratory alkalosis and perhaps chronic respiratory acidosis.So if it looks like predominately a metabolic acidosis or metabolic alkalosis, but if the pH is normal, there is likely another acid base disorder present
59 Acid-BaseMetabolic acidosis with normal serum anion gap can be due to:1) GI losses of HCO32) Renal tubular acidosis
60 Renal Tubular Acidosis Hopefully will not need this.Normal renal response to acidosis is to increase ammoniagenesis and more NH4+ will be found in the urineFor those with close to normal GFR, the “urine anion gap” is a way to estimate urinary NH4+Urine anion gap = urine (Na+ + K+ – Cl-)If it is positive there is decreased NH4+ production and likely a renal component to the acidosisSince NH4+ is positively charged, each molecule of NH4+ must be accompanied by a negative charge which is almost always Cl-.In the case of a normal renal response to acidosis:A large amount of Cl- will accompany a large amount of NH4+Since NH4+ is not measured, the high Cl- will give a negative answer to the equation
63 Proteinuria Albumin vs. other protein Dipstick tests albumin Light chain is not detected by dipstick
64 PROTEINURIA Quantitative: 24 hour collection ACR: random albumin to creatinine ratioPCR: random protein to creatinine ratioMany use ACR and PCR instead of 24 h urine for urinary protein quantification because 24h collection can be inaccurate and is cumbersome, but these ratios may also be unreliable.
65 PROTEINURIA Microalbuminuria: less than dipstick albumin Can use albumin to creatinine ratio on random urine sample… best done with morning urine sample
66 Random Urine 24h Urine ACR (g/mol) Albumin (mg/24h) PCR Protein Normal F<2.0<2.8<30<20<200Micro-albuminuria2.0-302.8-3030-300Macro-albuminuria>30>300In practise, most nephrologists are of the opinion that microalbuminuria in the absence of diabetes does not indicate significant renal diseaseOn the other hand, microalbuminuria is a marker for cardiovascular mortality in population based studies
67 PROTEINURIA Is there persistent proteinuria or transient? Need to rule out transient proteinuria as it is common and does not usually develop into anything.Orthostatic proteinuria, (proteinuria only when upright, no significant protein when supine), can occur in young people, (<25 years old), and is also not usually indicative of any renal disease.
68 Quiz Question 3 The definition of nephrotic syndrome includes: : HypolipidemiaLipiduria24 hr protein ≥2ghypertension
69 Nephrotic Syndrome Definition: > 3 g proteinuria per day Edema HypoalbuminemiaHyperlipidemia and lipiduria are also usually present
70 Nephrotic Syndrome Causes: Secondary: DM, lupus Primary: Minimal change diseaseFSGSMembranous nephropathyNephrotic Syndrome tells you that you are dealing with glomerular disease
71 Nephrotic Syndrome Complications: Edema Hyperlipidemia Thrombosis…esp with membranous GN and very low serum albuminMost do not prophylactically anticoagulate for membranous GNIn those with membranous nephropathy who have a sudden severe and unexpected decrease in GFR, many experts think renal vein thrombosis should be ruled out usually with doppler studies.
72 Nephrotic Syndrome Treatment: Treat cause if possible Treat edema, lipidsTry to decrease proteinuriaGeneral measures to decrease proteinuria would be: BP control, use of ACE or ARB
74 Hematuria Significance: ≥3 RBC's per hpf DDx: Is it glomerular or not? RBC castsDysmorphic RBCs in urineCoinciding albuminuria may indicate glomerular disease
75 Hematuria Other investigation: Imaging of kidneys Serum creatinine Age over rule out urologic bleeding, i.e. urine cytology and referral for cystoscopyAlso need to rule out TCC of collecting system with risk factors such as smoking, previous cyclophoshamide
76 Hematuria For glomerular hematuria without proteinuria DDx includes: IgA nephropathyThin GBM diseaseHereditary nephritisIgA is not usually inherited. If proteinuria, hypertension or decreased GFR is present will likely be future deterioration in GFR.Thin GBM disease is often autosomal dominant. Usually does not cause any drop in GFR but does in some families.Hereditary nephritis is most often X-linked recessive and called Alport syndrome: affected males usually need renal replacement therapy by age 50. Associations are sensorineural deafness, eye changes.
86 TTKG? Requirements: [urine K+ (urine osmol/serum osmol)] serum K+ Urine osmolality > 300Urine Na+ > 25Reasonable GFRTTKG =U/P K+/U/P Osm[urine K+ (urine osmol/serum osmol)]“Trans tubular potassium gradient”This formula relates to the basic physiology of K secretion from principal cells.It is interesting to use it clinically if GFR is relatively normal but it is no longer regarded as being valid or helpful.serum K+<7, esp < 5 = hypoaldosteronism
87 AKIEven the term ‘AKI’ should not be on the exam…..