Approach to Proteinuria

Prof. Joshua K. Kayima

University of Nairobi
 SPECTRUM OF PROTEINURIA
Overflow proteinuria
• Light-chain excretion in MM
̶Other situations
• Lysozyme – leukemic cells
• Negative for albumin but protein detected by other
methods [eg. Urine Alb/Prot ratio; Bence Jones]
 SPECTRUM OF PROTEINURIA
[Contd.]
Tubular Proteinuria
• Low grade < 2g/day

• Albuminuria + tubular proteins , 2

microglobulin
 Glomerular Proteinuria
Functional ̶transient
Non nephrotic
̶Fever, exercise, CCF hyperadrenergic hyper-
reninemic states
Orthostatic ̶non nephrotic only day time < 1g/ 24hrs
̶Night sample clear
Fixed ̶non nephrotic
(persistent) Micro- (moderately increased)
Macro- (severely increased)
̶Nephrotic
Glomerular Proteinuria Significant
– > 1g – Albuminuria
+ casts– RBCs

– Coarse granular
+ hematuria (glomerular)
 Methods of detection
• Routine dipstick analysis
−Not sensitive enough for small amounts
• 24 hour collection “Gold Standard” -cumbersome
• Spot Urine Albumin – creatinine ratio (UACR)
−Corrects for variations in urine concentration due to
dehydration
−More convenient
−Correlates well with 24-hour collection in adults
 Definition of abnormalities in
albumin excretion
Category ACR mg/g Mg/mmol Term

A1 < 30 <3 Normal to mild increase

A2 30 – 300 3 – 30 Moderately increased

(micro-albuminuria)
A3  300 > 30 Severely increased (macro-albuminuria)

> 2200 > 220 Nephrotic range

• The albumin level should be looked at as a continuum where

risk is proportional to level rather than strata category
 Protein – to – creatinine ratio
(PCR)
• Usually similar results to ACR
• PCR should be requested in pregnancy and
where non-albumin proteinuria is suspected
• Adult < 15mg/mmol (< 150mg/g)
• In pregnancy  30mg/mmol ( 300mg/g) is
significant proteinuria
High PCR with normal ACR
e.g. light chain disease MM renal tubular disease
 Proteinuria - associations
Important indicator of renal disease
Indicator of risk for progression of kidney
disease
Increased risk of artherosclerosis and left
ventricular abnormalities
Contributing to increased
cardiovascular morbidity and mortality
Proteinuria – associations (cont’d)
• Correlates with presence of LVH in hypertensives
• Predicts increased risk of CV morbidity and
mortality in those with or without HTN
• Prognostic in heart failure patients
• Higher incidence of Coronary Artery Disease,MI,
• Better predictor of stroke risk in patients with
CKD than eGFR
 PROGNOSIS of PROTEINURIA
• Depend on
i) The cause of proteinuria (eg SLE)
ii) Duration of proteinuria
iii) Degree of proteinuria
 Albuminuria
• Albumin is the most common type of protein in
urine
• Persistent = increase in urine protein – 2 tests
over 3 or more months is the principal marker of
kidney damage.
• It is an early and sensitive marker in many types
of kidney disease
 Moderate excretion
(microalbuminuria)
1) Recognised independent risk factor for
cardiovascular disease in general population
hypertensive diabetics
2) Most significant factor for predicting morbidity
and mortality in patients with cardiovascular
disease and peripheral vascular disease.
3) Established association with progressive renal
disease in patients with diabetes
 In hypertension
• Prevalence 11 – 40%

• Prevalence increases with age and duration of

hypertension patients with microalbuminuria have
higher incidences of cardiovascular outcomes
compared with normo-albuminuric subjects.
 In diabetes type 1 & 2
• 10 – 42% develop microalbuminuria
• Related to duration of diabetes microalbuminuria
predicts early mortality
• Important risk factor for cardiovascular disease.
• Macroalbuminuria increases risk of
cardiovascular death 10 fold microalbuminuria
increases risk of cardiovascular death 1.2 fold
 In general population
• Microalbuminuria 6.1% men
USA
9.7% women

5 – 7% Europe
 Glomerular Diseases
1. Various diseases affect the glomerulus. They
could be inflammatory or non-inflammatory

2. Diseases lead to alterations in

-glomerular permeability. [Proteinuria] ;
-structure [Histology];
-and function [GRF].
 [Contd.] Glomerular Disease
• Glomerular disease can be primary [restricted in clinical
manifestation to the kidney, with unknown cause]
• Or secondary (secondary to known primary conditions or
part of a multisystem disease)
−eg SLE
−Vasculitis
−HIV / HBV / HCV
−Diabetes mellitus
 Disease expression.

The hallmark of glomerular disease is the

excretion of protein and/or RBCs in urine
• Presentations
−Asymptomatic urinary abnormalities
−Acute glomerulonephritis
−Rapidly progressive glomerulonephritis
−Chronic glomerulonephritis
−Nephrotic syndrome.
−(Overlap syndromes)
 Nephrotic syndrome
• Proteinuria (Key component)
>3.5g/1.73m2/24 hrs
Practice >2.5 – 3g/24 hr
Paed: > 40mg/hr per m2
• Hypoalbuminaemia
• Anarsarca
• Hyperlipidemia
• Hypercoagulability
 Various complications
• Metabolic and other complications are generally 2° to proteinurIa
• Hypoalbuminaemia
• Dyslipidaemia
• Hypercoagulability
• Infection
• ‘Transport-protein’ loss
• Anaemia risk
• Growth and development-delay
• Mineral-bone disease
• Hypovolaemia
 Risk of Infections
•  1g G (loss in urine)
•  catabolism of 1g
• Loss of complement factor B
• Large fluid collections
• Fragile nephrotic skin
• Dilution of local humoral immune factors
• Zinc and transferrin loss (required in lymphocytic function)
• Impaired neutrophil phagocytic function
• T-cell dysfunctions
• Immunosuppressive agents
 “Transport – Proteins” Loss

• Transferrin - microcytic anaemia

• Cholecalciferol - binding protein
- Vit D deficiency,
- Hypo Ca++
- 2o hyperparathyroidism
• Thyroxine - binding globulin
- depressed thyroxine levels
• Protein-bound drugs
changed pharmaco-kinetics
 Anaemia Risk
• Urinary Iron loss

• loss of trasferrin (transport protein)

• Impaired biosynthesis of Erythropoietin

• Concurrent ACE inhibitor therapy

Growth & Development Delay with
Active nephrotic
 Ascites – (untreated)
Associated with:

• Venous Dilation – of abdominal wall

• Umbilical hernia
• Rectal prolapse
• ↑ Respiratory difficulty
• Scrotal/labial pain
• Anasarca
 Treatment Goal
• Induce prompt remission

• Minimize complications and subsequent

mortality
 Approach to Solving Problems for the
Nephrotic Patient
Search, identify, deal with:
Glomerular injury.
-Manage any secondary causes of glomerulopathy
-Corticosteroids, immunosuppressive agents, -
monoclonal Ab
-Associated hypertension
-Stage of CKD
 Approach to Solving Problems for the
Nephrotic Patient
2. Oedema – Symptomatic

• Care for intravascular volume

• Loop diuretic? Spironolactone?, thiazides?,
bed rest?
• ?Albumin infusion
 Approach to Solving Problems for the
Nephrotic Patient
3. Infections
• Care –(aseptic technique)
• Search for (septic screen)
• Antibiotics
• ? Immunisations ( influenza, pneumococcal,
HBV, varicella)
• Immunoglobulins (with exposure)
• Isolation (epidemics)
Approach to Solving Problems for the
Nephrotic Patient

4. Hyperlipidaemia
• “Statins” – lipid lowering agents
(HMGCoA reductase inhibitors)

5. Hypercoagulable State
• Anticoagulants
- Heparin
- Warfarin
 Approach to Solving Problems for the
Nephrotic Patient
6. Malnutrition
• Nutritional assessment
• High protein diet

7. Bone Disease
• Vit D, Ca++ suppl
• Bisphosphonates (osteoporosis)
 Approach to Solving Problems for the
Nephrotic Patient
8. Proteinuria
• Angiotensin Converting Enzyme (ACE)
inhibitors OR
• Angiotensin Receptor blockers (ARB)
• Sodium-Glucose co-Transporter 2
(SGLT2) inhibitors.
• MRA – Eplerenone, spironolactone,
finerenone
• GLP-1receptor agonists- semaglutide