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- Why does he not have many complaints when he has so many complications?

There were not complaints because patients in G1-G3 are usually asymptomatic. Derangements in endocrine and organ function do not manifest at this stage.

- What is building up and causing the itchy skin?

There is uremic puritis as a complication of CKD: buildup of phosphate, calcium or PTH. In this patient it was high phosphataemia and PTH.

- What is causing the lethargy and vomiting?

Can be a complication of anemia. Vomiting is due to effects on GI tract.

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- Definition:
--> A progressive loss of renal function ovr time. gradual decrease in GFR and creat. clearance. Decline of function for three or more months, and GFR of less than 60 ml/min/m2
- Stages:
--> based on filtration rate as seen on left side of table. Has five stages from "high and optimum" down to "kidney failure"

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Causes

1. Hypertension

1. Glomerular & vascular changes

2. Interstitial nephritis

3. → Nephron loss

Elevated blood pressure leads to hypertrophic responses in large and small vasculature. Can lead to long-term glomerular damage, although it is compensatory at first. All leads to nephron and tubular damage, which leads to decreases in kidney function. Nephritis leads to the atrophy of tubules. chronical hypertension leads to nephrons loss and function.

1. Diabetic nephropathy

1. Chronic hyperglycemia

2. Glomerular hyperfiltration

3. Hyperglycemia and AGE

4. Cytokines

Glomerular hyperfiltration and hyperglycemia leads to diabetic nephropathy, glomerular sclerosis and eventually nephron loss.

1. Other

See table below

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Once half of total nephrons are lost, pathogenesis of CKD is the same regardless of cause.

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nephrotoxic inflammation = sclerosis

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1. Urinalysis

Look whether there is blood or proteins in urine. Which would suggest if there is a present glomerular disease or not.

24 hour urinalysis would suggest the urinary production per day as a function of fluid intake per day. The patient case had normal output, but had a leakage of protein over 24h (6-fold the normal protein levels)

1. Urine microscopy

White cells (pyuria) can indicate UTI, eosinophiluria (allergic nephritis), casts which form from abnormal cells in tubular lumen, red cell casts which can suggest glomerular nephritis. RBCs can come anywhere from glomerulus to urethra.

1. Urine biochemistry

Measure of urinary electrolytes, Urinary Na+ can be useful. Urine osmolality indicated the kidney concentration ability.

Low urine osmolality normal with high fluid intake, abnormal when the body must concentrate urine (i.e. hypovolemia).

Urine electrophoresis and immunofixation → necessary for detection of light chains, which can be present without detectable serum paraprotein

1. Serum biochemistry

Urea and creatinine

eGFR

Electrophoresis and immunofixation for myeloma

Rhabdomyolysis: suggested by high creatinine kinase and disproportionate elevation in serum creatinine and potassium compared with urea

1. Hematology

Eosinophilia → suggests vasculitis, allergic tubulointerstitial nephritis, cholesterol embolism.

Marked raised viscosity → suggests myeloma or vasculitis (blood vessel inflammation)

Fragmented RBCs and/or thrombocytopenia → suggest intravascular haemolysis due to accelerated hypertension, haemolytic uremic syndrome or thrombotic thrombocytopenic purpura.

Tests for sickle cell disease → performed when relevant.

1. Immunology

Complement components → may be low in active renal disease due to SLE?

Autoantibody screening → useful in detection of numerous autoimmune diseases.

Cryoglobulins → prevalent in unexplained glomerular disease.

Antibodies to streptococcal antigens →

Antibodies to hepatitis B and C → may point to polyarteritis or membranous nephropathy.

Antibodies to HIV → raise possibility of HIV-associated renal disease.

is a complication of HIV infections.

1. Radiological investigation

Ultrasound → every patient for renal size and hydronephrosis assessment.

CT → low density renal stones/nephrocalcinosis (can be missed by ultrasound), retroperitoneal fibrosis, urinary obstruction, cortical scarring.

MRI  → MR angiography in renovascular disease. Must be careful with contrast agents as some can cause kidney injury.

1. Renal biopsy

Done in patients with unexplained CKD and normal sized-kidneys

Unless there are strong contra-indications.

Must be performed within 24-hour is there is suspected glomerular nephritis.

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1. Anemia

Related to the kidney function loss of erythropoetin (defficiency). There are also Fe, Vit. C, RBC destrcution, blood loss etc.

1. Renal osteodystrophy

Refers to bone mineral disorder and embraces various forms of bone disease that can develop independently or along with CKD, hyperparathyroid bone disease, osteomalacia, osteoporosis, osteosclerosis and adynamic bone disease.

→ most CKD patients have histological findings compatible with mixed bone disease (see figure 22-3 below)

Bones are constantly being remodelled, as they are our calcium reservoir. This cycle of remodelling depends on Vit. D

a lack of Ca and Vit. S will lead to Calcium reabsoprtion without bone remodelling. Ultimately leading to decreased bone quality and function.

In chronic kidney failure, bone disease is common.

In menopause, bone homeostasis is also altered due to endocrine changes.

PTH controls calcium and phosphate homeostasis.

as patient's Ca is low, it signals an increase production of PTH in order to regulate it. Feedback loop --> secondary Parathyroidism.

Primary hyperparathyroidism would be due to a problem with the PT gland itself (i.e. tumour)

1. Skin disease

Pruritus is common in severe CKD and is mainly due to retention of nitrogenous waste products of protein catabolism

Inadequate dialysis is the commonest cause of pruritus.

Other causes of pruritus include:

Hypercalcemia

Hyperphosphatemia

Elevated Calcium x Phosphate product (CaxPi)

Hyperparathyroidism

Fe deficiency

Numerous CKD patients suffer from dry skin → treated with simple aqueous creams.

Eczematous lesions are common in relation to region of AV fistulas

1. Nephrogenic systemic fibrosis

Systemic fibrosis disorder, primarily involving skin. Moderate to severe CKD patients and patients on dialysis. Caused with certain contrast agents.

1. Gastrointestinal complications

Decreased gastric emptying, increased reflux, increased risk of peptic ulcers.
- common in patients with continuous ambulatory peritoneal dialysis.

1. Metabolic abnormalities

Insulin is catabolized by kidneys --> insulin requirements in diabetic patients decrease and CKD progresses. In advanced CKD, patients become more resistant to insulin.

Lipid abnormalities are very common in CKD patients. Can lead to complications in ESKD.

1. Endocrine abnormalities

Hypoprolactinin anaemia, galacturea, increased LH, decreased testosterone, erectile dysfunction and decreased spermatogenesis. CKD can have negative effects on hormones at systemic levels.

1. Muscle dysfunction

Uremia disrupts normal muscle energy metabolism.

1. Nervous system

CNS: severe uremia can cause depressed cereb function and increased seizure. Can lead to dialysis dementia as progressive neurogenic degeneration occurs. There is also onset of psychiatric signs.

Autonomic NS: impaired afferent vagal function, overactive symp. system (HT), improve after dialysis and transplantation.

PNS: median nerve compression and carpal tunnel syndrome. Polyneuropathy when patients inadequately dialysed.

1. Calciphylaxis

Rare complication that is commonly seen in CKD patients (has poor prognosis). Contributes to death of dialysis patients. Presents as painful non-healing eschars (superficial wounds in non-motile patients), dermal necrosis. Histology suggests calcification of vascular system and small vessel thrombosis.

1. Cardiovascular disease

Life expectancy of CKD patients remains severely reduced compared to normal population due to increased incidence (16-fold) of CV disease, particularly MI, cardiac failure, sudden cardiac death and stroke.

Risk Factors

Hypertension frequent complication of CKD

Diabetes mellitus is the commonest CKD cause.

Dyslipidemia is universal in uraemic patients.

Ventricular hypertrophy is common, along with systolic and diastolic dysfunction.

Diastolic dysfunction highly attributable to left ventricular hypertrophy →  Contributes to hypotension during fluid removal in hemodialysis.

Systolic dysfunction may be due to:

Myocardial fibrosis

Abnormal myocyte function owing to uraemia

Ca2+ overload and hyperparathyroidism.

Carnitine and selenium deficiency.

Left ventricular hypertrophy risk factor for early CKD death.

Hyperparathyroidism → can contribute to pathogenesis by increasing intracellular calcium

Vascular Calcification → VC during uremia is thought to be an active process where vascular smooth muscle cells acquire osteoblast-like characteristics in response to increased phosphate levels.

Inflammation → potent mediator of vascular calcification by inhibition of fetuin

Raised CaxPi product → causes medial calcification

1. Pericarditis

Uremic pericarditis: a feature of pre-terminal uremia or inadequate treatment. Atrial arrythmias, pericardial tamponade.

Dialysis pericarditis: can be cause by surgery in a patient when  they are receiving adequate dialysis.

1. Malignancy

ADPKD

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1. Renoprotection

Drug approach to renonephroapthies. Goals are to manage HT and protein levels in the urine. (See box 12.6 below). Only in patients with less than 1g of proteins. Used when CKD has not significantly progressed. --> increased risk can be kept under control.

1. Treatment of complications (summarized with box 12.6)

1. Hyperkalemia

2. Acidosis

3. Calcium and phosphate control & suppression of PTH

1. Treatment

1. Early referral

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1. Hemodialysis

When blood of patient is pumped through set of semi-perm. membranes, bringing the blood into close contact with dialysate, where particles in excess flow out. Blood then flows back into patient. Dialysate can be adapted dependent on individual gradients per patient.

1. Hemofiltration

Plasma water is removed, calcium, phosphate etc. And is replaced with solution of desired composition. Principle is still with semipermeable membrane. Employs counter-convenction, whereas dialysis employs convection. Removes larger particles like proteins that cannot be removed by haemodialysis.

1. Peritoneal dialysis

Dialysis that employs the peritoneal membrane as natural filter, where dialysate is pumped into peritoneal space and removes undesired serum products through differential concetration gradients. Is tolerated more by patients, cheaper, is less effective than haemodialysis but has high risk of infection. Therefore requires large patient complicance with hygiene measures.

1. Transplant

Success of transplantation depends on:
- Blood compatibility (HLA)
- Immunosuppresive treatment
- Donor kidneys are ideally acquired from family.
- Cadaver transplants as well --> immunosuppresion.

Complications include:
- Tubular necrosis as most common cause of graft complications.
- Technical failures.
- Acute rejection.
- Infections
- Malignancy

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1. What is the function of parathyroid hormone?

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1. source: https://www.ncbi.nlm.nih.gov/books/NBK499940/

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To compensate for the low calcium due to low Vitamin D levels, the parathyroid glands increase the parathyroid hormone secretion. This leads to a high bone turnover, always attempting to normalize the low calcium levels in the blood. Over time, this becomes maladaptive leading to extraosseous calcification, and parathyroid hyperplasia develops (tertiary hyperparathyroidism).

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Summary

Chronic kidney disease is a general term for heterogeneous disorders affecting kidney structure and function. The 2002 guidelines for definition and classification of this disease represented an important shift towards its recognition as a worldwide public health problem that should be managed in its early stages by general internists. Disease and management are classified according to stages of disease severity, which are assessed from glomerular filtration rate (GFR) and albuminuria, and clinical diagnosis (cause and pathology). Chronic kidney disease can be detected with routine laboratory tests, and some treatments can prevent development and slow disease progression, reduce complications of decreased GFR and risk of cardiovascular disease, and improve survival and quality of life. In this Seminar we discuss disease burden, recommendations for assessment and management, and future challenges. We emphasise clinical practice guidelines, clinical trials, and areas of uncertainty.

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Chronic kidney disease is a general term for heterogeneous disorders affecting kidney structure and function. The 2002 guidelines for definition and classification of this disease represented an important shift towards its recognition as a worldwide public health problem that should be managed in its early stages by general internists.

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Chronic Kidney Disease (CKD)  Pathophysiology

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989826/pdf/jcad_1_2_38.pdf