CKDUSJP

Chronic kidney disease







Objectives:

• Definition of CKD
• Pathophysiology & progression
• Staging of CKD
• Aetiology
• Clinical features
• Consequences of CKD
• Investigations
• Management

What is chronic kidney disease?
Chronic kidney disease is defined as either kidney damage or GFR < 60ml/min/1.73M² for over 3 months.
Kidney damage is defined by pathologic abnormalities or markers of renal damage.

Pathophysiology of CKD

• Histology is characterized by progressive destruction of renal mass with irreversible sclerosis of nephrons. 
• There is a gradual impairment of excretory, metabolic and endocrine functions of the kidney eventually leading to end stage renal failure. 

Progression of chronic kidney disease

• Kidney responds to nephron loss by compensated glomerular hypertrophy and glomerular hyperfiltration. When glomerular hyperfiltration is long standing it can lead to further loss of nephrons. Therefore once the damage occurs, the renal impairment gradually progresses to end  stage renal disease.

• There is a large amount of reserve renal function. Up to 70% of the renal mass can be lost and still the kidney can maintain homeostasis.
  The patient become symptomatic when GFR declines below 30% and ESRF is when renal function is less than 10-15%.

Staging of CKD

The stages of CKD are  based on glomerular filtration rate. There are five stages; from normal  kidney function  in stage 1 and minimally reduced in stage 2 to kidney failure in stage 5.  

eGFR Calculation

Use Modified Diet in Renal Disease equation (MDRD Equation).

https://www.kidney.org/professionals/kdoqi/gfr_calculator

Learning Exercise: 

A 30-year-old Sri Lankan man is diagnosed to have CKD. His serum creatinine is 3.8mg/dl. What is his eGFR? 

Aetiology of CKD

      Some of the common causes are listed below

•         Diabetes Mellitus (commonest cause world wide)

•         Hypertension

•         Chronic glomerulonephritis

•         Chronic pyelonephritis

•         Chronic interstitial nephritis

•         Polycystic kidney disease

•         Obstruction

•         Systemic diseases; SLE

•         Unknown

Clinical features

Symptoms depend on the stage of the disease.

In early stages of CKD most patients remain asymptomatic. 

•         Ill health

•         Nocturia, polyuria

•         Oedema; ankle & facial swelling

•         Anorexia, nausea

•         Pruritus

•         Anaemia

•         Pigmentation

•         Brown arc in finger nails

•         Hypertension

•         Peripheral neuropathy

•         Renal osteodystrophy

•         Features of severe uremia

Ø Acidotic breathing

Ø Flapping tremors

Ø Pericarditis
Ø Drowsiness, convulsions and coma

Half-and-half nails in CKD 

http://redbeans.tulane.edu/wp-content/uploads/2015/05/lindsays-nails.jpg

Why anaemia develops in CKD?

Anaemia in CKD is due to multiple factors

• Most important reason is deficiency of erythropoietin production   causing normocytic normochromic anaemia.

• Dietary deficiency can be due to anorexia and dietary restrictions. This can lead to iron def. anaemia

• Haemorrhagic tendency

• Tendency for haemolysis

•  Bone marrow suppression due to uremic toxins

What are the electrolyte and metabolic problems?

1. Hyperkalemia

• is due to impaired ability of kidney to excrete K⁺ load 
• Hyperkalaemia is the most life threatening electrolyte problem in CRF
•  

2. Low serum bicarbonate

• Decreased ability to reabsorb HCO3

3. Metabolic acidosis with high anion gap

What is renal osteodystrophy?

Renal osteodystrophy is a mixture of osteomalacia, parathyroid bone disease (osteitis fibrosa)  and osteoporosis.

There is  Po₄⁺ retention in CKD . Due to deficiency of 1,25 dihydroxy-cholecalciferol , absorption of Ca⁺ is impaired.  Both High Po₄⁺ & Low Ca⁺ stimulates the parathyroid gland to secrete excess parathyroid hormones.

 

What are the relevant investigations in a patient with CKD?

1)     Urine full report  – Presence of protein, red blood cells and rbc casts indicates underlying glomerular disease

2)     Renal function assessment

a.   serum creatinine

b.    e GFR 

3)     Serum electrolytes – look for hyperkalaemia

4)     Full blood count and  blood picture -  normochromic normocytic in erythropoietin deficiency / or evidence of Fe deficiency

5)     Serum calcium, phosphate

6)     ECG - LV hypertrophy secondary to hypertension, changes of hyperkalaemia

7)     Chest X ray

8)    Cardiovascular risk factors: Lipid profile, blood sugar

10) Arterial blood gas analysis

11) Renal ultrasound

a.       To assess kidney size (Small size kidneys)

b.       To exclude obstructive uropathy

c.       To diagnose underlying disease such as PCKD

d.       Renovascular disease

What is the Management? 

Patients with CKD should be referred to a nephrologist/specialist at the appropriate time for further evaluation. 

Therapeutic strategies depend on the stage of CKD and include

Specific therapy for underlying disease

–     Slowing the loss of kidney function

• Treatment of underlying disease, 
•  protein restriction,
•  control of hypertension
•  ACEI therapy are shown to retard the progression of disease process.

–     Prevention and treatment of cardiovascular disease

–     Prevention and treatment of complications of decreased kidney function

–     Preparation for kidney failure and kidney replacement therapy

–     Replacement of kidney function by dialysis and transplantation

1)   Diet

     - Protein restriction (0.8 – 1.0 g/kg body weight) is recommended. This reduces  production of N₂ waste products and decline of renal function. --Severe protein restriction can lead to malnutrition and patient compliance can be poor on protein restriction

   -  Na⁺ restriction in oedematous or hypertensive  patients,

    -   K⁺ restriction:   https://draxe.com/top-10-potassium-rich-foods/
    -   Po₄ restriction: https://www.kidney.org/atoz/content/phosphorus

Learning Exercise: Learn food that contains high potassium and high phosphate in Sri Lanka which enable you to give dietary advice.   

2)   Treatment of hypertension

- Consider blood pressure target of f ≤ 130/80 mmHg. 

- Choice of drugs depend on patient tolerance, associated co-morbid conditions. 

- ACEI or receptor blockers are preferable. 

- Most patients require more than one drug. Other drugs are diuretics (Frusemide), Ca channel blockers, ß blockers, Methyl dopa and prazocin.

- Thiadizides are not effective when GFR is low.

3)   ACEIs / ARB therapy

- ACEI and ARBs have been shown to retard the progression to ESRD.              - Beneficial in both diabetic and non-diabetic renal disease. 

- At the start of therapy there is a risk of a deterioration of renal function.      - Hence needs close monitoring of serum creatinine.  

- Hyperkalaemia can be a problem in the presence of renal failure.

4)   Control of blood sugar

- Good glycaemic control may prevent the development of diabetic nephropathy.

- Patients with advanced renal disease need modification of their insulin and oral hypoglycaemic therapy.

5)   Treatment of anaemia.

- Renal failure leads to normocytic anaemia due to erythropoietin deficiency. 

- Most effective treatment is erythropoietin (Human Recombinant Erythropoietin) 4000 iu weekly to maintain Hb at 10g/dl. 

Iron intake should be maintaine with oral/iv supplements.

- Any other dietary deficiencies if present should be treated. 

- Blood transfusions should be avoided or kept to minimal due to HLA reactivity and risk of CMV transmission. CMV infections can cause problems during post transplant immunosuppression.

6)    Prevention of Renal osteodystrophy   

- Renal osteodystrophy is due to increase in parathyroid hormone as a result of hypocalcaemia and hyperphosphatemia. .

- Initial step is to  control hyperphosphatemia by dietary measures and use of phosphate binders. Most agents binds  Po₄  efficiently in the gut. Calcium carbonate is  commonly available . Sevelamer hydrochloride and Lanthanum carbonate are other agents.

-  1,25 dihydroxycalciferol and calcium supplements should be given to correct hypocalcaemia. 

- If facilities available serum parathyroid hormone levels should be checked.

7)   Correction of cardiovascular risk factors

Cardiovascular disease is a major cause of mortality in CKD patients. Therefore correction of cardiovascular risk factors is a major part of management and should include smoking cessation,  weight loss, aerobic exercises and treatment of hyperlipidaemia. Lowering of LDL cholesterol to < 100 mg/dl is recommended.

8)   Other Rx

–       Avoid nephrotoxic drugs

•         Gentamicin, contrast agents, NSAIDs

–       Avoid drugs that can cause hyperkalaemia

•         Spiranolactone, amiloride

–       Adjust the dosage of certain medications

•         Digoxin

–       Avoid dehydration during intercurrent illnesses such as diarrhoea and vomiting

Adverse outcomes of chronic kidney disease can often be prevented or delayed through early detection and treatment.

9)   Renal replacement therapy

In End stage renal disease (ESRD) life can no longer sustained with conservative therapy alone. These patients should be assessed for renal replacement therapy.

–       Long term dialysis - Peritoneal dialysis or Haemodialysis

–       Renal transplantation -Live donor transplantation/ Cadaveric  transplantation

Large percentage of patients with CRF are young and in their productive years of life. RRT is expensive. Early diagnosis and implementation of measures to prevent further deterioration is the cornerstone of management.