1. Back to Basics Nephrology 2013
Major issues in Nephrology, Electrolytes, Acid-base disturbances

2. CKD

3. K/DOQI Classification of Chronic Kidney Disease
Stage GFR (≥3mo) Description
(ml/min/1.73m2)
 Damage with normal GFR
Mild  GFR
Moderate  GFR
Severely  GFR
< Kidney Failure
This 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.
Approximately 500,000 Canadians have stage 3 CKD; most of these will not need renal replacement therapy
The presence of proteinuria is a very important marker that predicts future decrease in GFR and cardiovascular mortality

4. In this K/DOQI staging, “kidney damage” means:
Persistent proteinuria
Persistent glomerular hematuria
Structural abnormality:
such as PCKD, reflux nephropathy

5. CHRONIC KIDNEY DISEASE
Diagnosis:
Acute vs. chronic:
Small kidneys on U/S or unenhanced imaging mean CKD
Diabetic CKD may still have normal sized kidneys
Some other causes of CKD and normal sized kidneys are myeloma, amyloid, and polycystic kidney disease

6. CHRONIC KIDNEY DISEASE
Common causes of CKD:
Diabetic nephropathy
Vascular disease GN
PKD
GN, (glomerulonephritis) here means glomerular disease due to primary or idiopathic causes other than secondary disease such as diabetic nephropathy.

7. CHRONIC KIDNEY DISEASE
Causes of CKD:
Best to divide as proteinuric or non-proteinuric CKD
Proteinuric is much more likely to have deterioration in GFR and higher cardiovascular morbidity and mortality

8. CHRONIC KIDNEY DISEASE
Treatment
Delay progression:
Treat underlying disease i.e. good glucose control for DM
BP control to 140/90, (the current target); 130/80 for diabetics
ACEI or ARB has extra benefit for proteinuric CKD
Lower protein diet…maybe
BP target guidelines are constantly changing. These are from 2012 Canadian Hypertension Education Program.

9. CHRONIC KIDNEY DISEASE
Treatment of the consequences of decreased GFR:
PO4:
decrease dietary intake
PO4 binders such as CaCO3
Hypocalcemia:
CaCO3, 1,25 OH D3
Hyperphosphatemia and hypocalcemia typically does not occur until GFR falls below 30 ml/min
Typical dietary sources of PO4 are dairy, meat, colas
With 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 substances such as sevalemer), is used to bind PO4 in the GI tract and prevent it from being absorbed
Active 1,25 OH D3 is 1 hydroxylated in the kidney, 25 hydroxylated in the liver

10. CHRONIC KIDNEY DISEASE
Treatment of the consequences of decreased GFR:
Anemia:
Erythropoetin current target Hb
Anemia in CKD does not usually occur till GFR is less than 30 ml/min
Studies have shown increased mortality with targeting Hb closer to normal values and opinion re: target Hb varies

11. CHRONIC KIDNEY DISEASE
Uremic Complications:
Major:
Pericarditis
Encephalopathy
Platelet dysfunction
Uremic complications that are not life threatening include: nausea, vomiting, anorexia, prutitis

12. ARF

13. Urine values compatible with pre-renal failure:
Click here in slide show mode
Question 1
Urine values compatible with pre-renal failure:
Osm < 300 mosm/L
RBC casts
Na+ < 20 mmol/L
Fex Na+ > 2%

14. ARF
Pre renal and ATN most common causes (quoted at 70% of cases of ARF)
DDx:
Pre Renal
Intra Renal
Post Renal
The term AKI, (Acute Kidney Injury), is being used in clinical research settings in place of ARF
I 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.

15. Urine: Pre-Renal vs. Renal Assessment of Function
U Na U Osm Fe Na
Pre-Renal
ATN
< 20
> 500
< 1%
> 40
< 350
> 2%
U/P Na
U/P Cr
These values have been validated since the 1970s
The UNa, Uosm require that the patient be oliguric
The FeNa is much more predictive if the patient is oliguric
Fe Na =
X 100
Pigmented granular casts found in up to 70% of cases of ATN

16. Urine: Pre-Renal vs. Renal Assessment of Function
Fe Urea
Pre-Renal
ATN
< 35
U/P Ur
U/P Cr
Fe Urea =
X 100
> 55
Personally, my take on what is published is that the FeUrea is not predictive for prerenal ARF
FeUrea might be useful to Dx pre renal ARF in those who received diuretics…but not all studies support its use.

17. ARF
Investigations:
Pre Renal: Urine tests as noted and responds to volume
Intra-Renal: look for GN, interstitial nephritis as well as ATN
Post Renal: Imaging showing bilateral hydronephrosis is highly specific for obstruction causing ARF
Although 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.
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.

18. Dialysis: Who Needs It? If cannot control these by other means:
Hyperkalemia
Pulmonary edema
Acidosis
Uremia
(GFR < 10-15% for CRF)
NB in practice almost always, volume or hyperkalemia are the usual reasons to start dialysis in ARF
In ARF, dialysis has usually been started for volume or K before any uremic indications happen

19. Dialysis: Who Needs It?
Hemodialysis is also used for intoxications with:
ASA Li
Alcohols: i.e. methanol, ethylene glycol
Sometimes theophylline

20. Na+

21. Hyponatremia
Pseudo:
If total osmolality is high: hyperglycemia/ mannitol
If total osmolality is normal, could be due to very high serum lipoprotein or protein
The normal osmolality hyponatremia will happen only if Na is measured by the lab in a certain way, for example a flame photometer

22. Hyponatremia Volume status:
Hypovolemic: high ADH despite low plasma osmolality
High total volume: CHF/ cirrhosis have decreased effective circulating volume and high ADH despite low plasma osmolality

23. 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 ADH
If 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 problem
Normally, people can drink 10 to 15 L of water per day without causing hypo Osmotic plasma, but I would not recommend anyone try this

24. Hyponatremia Treatment: Hypovolemic: Decreased effective volume:
Replace volume
Decreased effective volume:
Improve cardiac output if possible
Water restrict
SIADH:

25. Hyponatremia Treatment: Rate of correction of Na:
Not more than 10 mmol in first 24 h and not more than 18 mmol over first 48 h of treatment
Or Central Pontine Myelinosis may occur
There 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

26. Potassium

27. Hyperkalemia Real or Not: Hemolysis of sample Very high WBC, PLT
Prolonged tourniquet time
ECG 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.

28. Hyperkalemia Shift of K from cells: Insulin lack
High plasma osmolality
Acidosis
Beta blockers in massive doses

29. Hyperkalemia Increased total body K: Decreased GFR plus:
High diet K
KCl supplements
ACEI/ARB
K sparing diuretics
Decreased Tubular K secretion

30. TTKG? Requirements: [urine K+  (urine osmol/serum osmol)] serum K+
Urine osmolality > 300
Urine Na+ > 25
Reasonable GFR
TTKG =
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 not clear how useful it is.
However, it has been known to be asked about on exams.
serum K+
<7, esp < 5 = hypoaldosteronism

31. Hyperkalemia Treatment IV Ca Temporarily shift K into cells: Remove K
Insulin and glucose
Beta 2 agonists (not as reliable as insulin)
HCO3 if acidosis present
Remove K
For modest hyperkalemia, many use kayexalate po given with a non absorbable sugar such as lactulose or sorbitol. Others argue that there is little evidence that it works.
If kayexalate is given as an enema, do not use lactulose or sorbitol as they can damage colonic mucosa.

32. GFR

33. ASSESSMENT OF GFR:
Creatinine concentration alone is not the best way to assess GFR

34. ASSESSMENT OF GFR: UCr x V PCr (140-age) x Kg x1.2 Creat
Creatinine clearance formula:
(140-age) x Kg x1.2
Creat
(x .85 for women)
Cockroft-Gault estimated Creatinine clearance
Need a Steady State for these to be valid

35. MDRD eGFR
Labs now calculate this for anyone who has a serum creatinine checked
Use serum creatinine, age, sex

36. MDRD eGFR
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 is
the exponential. The value obtained must be multiplied by if
the 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)
Do NOT memorize this formula

37. Limitations of GFR estimates: Not reliable for:
extremes of weight or different body composition such as post amputation, paraplegia
acute changes in GFR
use in pregnancy
eGFR greater than 60ml/min/1.73m2
As 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

38. Proteinuria

39. Proteinuria Albumin vs. other protein Dipstick tests albumin
Light chain is not detected by dipstick

40. PROTEINURIA Quantitative: 24 hour collection
ACR: random albumin to creatinine ratio
PCR: random protein to creatinine ratio
Many use ACR and PCR instead of 24 h urine for urinary protein quantification because 24h collection can be inaccurate and is cumbersome

41. PROTEINURIA Microalbuminuria: less than dipstick albumin
Can use albumin to creatinine ratio on random urine sample… best done with morning urine sample

42. Random Urine 24h Urine ACR (g/mol) Albumin (mg/24h) PCR Protein NormalF
<2.0
<2.8
<30
<20
<200
Micro-albuminuria
2.0-30
2.8-30
30-300
Macro-albuminuria
>30
>300
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.
In practise, most nephrologists are of the opinion that microalbuminuria in the absence of diabetes does not indicate significant renal disease
On the other hand, microalbuminuria is a marker for cardiovascular mortality in population based studies

43. Question 2 The definition of nephrotic syndrome includes: :
Hypolipidemia
Lipiduria
24 hr protein ≥2g
hypertension

44. Nephrotic Syndrome Definition: > 3 g proteinuria per day Edema
Hypoalbuminemia
Hyperlipidemia and lipiduria are also usually present

45. Nephrotic Syndrome Causes: Secondary: DM, lupus Primary:
Minimal change disease
FSGS
Membranous nephropathy
Nephrotic Syndrome tells you that you are dealing with glomerular disease

46. Nephrotic Syndrome Complications: Edema Hyperlipidemia
Thrombosis…with membranous GN and very low serum albumin
Most do not prophylactically anticoagulate for membranous GN
In 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.

47. Nephrotic Syndrome Treatment: Treat cause if possible
Treat edema, lipids
Try to decrease proteinuria
Measures to decrease proteinuria would be: BP control, use of ACE or ARB

48. Hematuria

49. Hematuria Significance: ≥3 RBC's per hpf DDx: Is it glomerular or not?
RBC casts
Dysmorphic RBCs in urine
Coinciding albuminuria may indicate glomerular disease

50. Hematuria Other investigation: Imaging of kidneys Serum creatinine
Age over rule out urologic bleeding, i.e. urine cytology and referral for cystoscopy
Also need to rule out TCC of collecting system with risk factors such as smoking, previous cyclophoshamide

51. Hematuria For glomerular hematuria without proteinuria DDx includes:
IgA nephropathy
Thin GBM disease
Hereditary nephritis
IgA 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
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.

52. Ca++, PO4, Mg++

53. Ca++ and PO4-- Decreased GFR and increased PO4 Decreased Ca
1 OH of 25-OHD3
Increased PTH
Renal osteodystrophy
Increased PO4 usually happens when GFR falls below 30 ml/min.
Increased plasma PO4 will cause a fall in plasma Ca
Decreased production of 1, 25 OH D3 usually occurs when GFR falls below 30 ml/min
Low plasma Ca results in a rise in PTH
PTH causes osteoclast mediated release of Ca from bone and also decreases tubular reabsorption of PO4
Renal osteodystrophy is a term used for the net effects of high PTH and low 1,25 OH D3 on bone and usually happens with very low GFR ie below 15 ml/min

54. Magnesium Hypomagnesemia: GI loss/lack of dietary Mg Renal loss:
Diuretics
Toxins esp cisplatin

55. Hypophosphatemia Shift Decreased total body PO4 Fanconi Syndrome?
GI loss/decreased intake
Renal loss
Fanconi Syndrome?
Very rare renal tubular loss of:
PO4, amino acids, glucose, HCO3-
Fanconi syndrome appears more often on exams than in real life

56. Question 3 Most likely cause of Na 140 Cl 110 HCO3 10 : RTA
serum albumin 20
resp alkalosis
ketoacidosis

57. Acid-Base Approach to: Resp or metabolic Compensated or not
If metabolic: anion gap or not
Anion 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

58. Acid-Base Increased anion Gap acidosis: “MUDPILES”: Methanol Uremia
Diabetic/alcoholic ketosis
Paraldehyde
Isopropyl alcohol
Lactic acid
Ethylene glycol
Salicylate

59. Acid-Base
Metabolic acidosis with normal serum anion gap can be due to:
1) GI losses of HCO3
2) 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 urine
For 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 acidosis
Since 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

62. AKI
Even the term ‘AKI’ should not be on the exam…..